Method and apparatus for neuromodulation treatments of pain and other conditions

ABSTRACT

Systems, devices, and methods for neurostimulation using a combination of implantable and external devices to treat pain are disclosed.

CROSS-REFERENCE

This application is a continuation of U.S. patent application Ser. No.16/408,989, filed May 10, 2019, now U.S. Pat. No. ______; which is acontinuation of U.S. patent application Ser. No. 15/385,729, filed Dec.20, 2016, now U.S. Pat. No. 10,335,596; which is a continuation of PCTApplication No. PCT/US2015/036821, filed Jun. 19, 2015; which claims thebenefit of U.S. Provisional Application Nos. 62/015,392, filed Jun. 21,2014; 62/053,085, filed Sep. 19, 2014; and 62/077,181, filed Nov. 8,2014; which applications are fully incorporated herein by reference.

The subject matter of this application is also related to the subjectmatter of U.S. Provisional Application No. 61/953,702, filed Mar. 14,2014 and entitled “Method and Apparatus for Versatile Minimally InvasiveNeuromodulators”, which application is fully incorporated herein byreference.

BACKGROUND

Neuromodulation treatments for chronic pain are known and are frequentlyused for treating patients. Most use large devices with batteries andlong leads to electrically stimulate nerves inside the body. Thesedevices require invasive implantation, which are very costly. They alsorequire periodic battery replacement, which requires additional surgery.The large sizes of these devices and their high costs have preventedtheir use in a variety of applications that have demonstrated effectiveneurostimulation treatments. Additionally, most of these devicesstimulate large areas of non-target nerves in addition to the desirednerves, which can have negative effects on the patient and reduce theefficacy of the therapy.

The therapeutic treatment of chronic or acute pain is the single mostcommon reason patients seek medical care, accounting for approximately50% of all physician office visits. Chronic pain in particular is oftendisabling with the associated economic impact estimated at over $100billion. A large portion (25% to 50%) of the population that is over theage of 65 suffers from health problems that predispose them to pain. Aneven greater portion (45%-85%) of the nursing home population suffersfrom chronic pain.

The primary treatments for chronic pain are pharmaceutical analgesicsand electrical/neurostimulation. While both of these methods providesome level of relief, they are not without their drawbacks.Pharmaceuticals can have a wide range of systemic side effects such asGI bleeding as well as interactions with other drugs, etc. Opioidanalgesics can be addictive and can they be debilitating. Also, theanalgesic effect provided by pharmaceuticals is relatively transientmaking them cost prohibitive, particularly for the aging population.

Neurolysis is a technique that is growing in popularity whereby aparticular nerve is temporarily damaged so that it can no longertransmit pain. One method gaining in popularity is the use ofneurotoxins such as botulinum toxin which must be used in large volumeson a regular basis and has a number of risks, side effects, andcontraindications associated with its use. Additionally, neurolysis isprimarily used to treat chronic pain, but may also have applications inacute pain under certain conditions such as those where a nerve block(such as an epidural) would be used.

Another method is the use of thermal injury from an energy source suchas radio frequency or cryoablation. The procedure is minimally invasiveand can be performed under local anesthesia. It has no systemic effectsand does not cause permanent damage; however, there are several aspectsof the existing technology available to perform such a procedure thatcould be improved upon.

Neurostimulators can be used for at least three different applications:neuromuscular stimulation, peripheral nerve stimulation, or spinal cordstimulation. The major drawback is that they must be surgicallyimplanted resulting in an expensive procedure which has serious risks,side effects, contraindications, and ongoing maintenance or upgrades.

Nerve stimulation treatments have shown increasing promise recently,showing potential in the treatment of many chronic pain conditions suchas neuromuscular stimulation, peripheral nerve stimulation, or spinalcord stimulation. Other conditions have also shown promise though are inmuch earlier stages, including drug-resistant hypertension, motilitydisorders in the intestinal system, and metabolic disorders arising fromdiabetes and obesity. The primary drawback is that they must besurgically implanted resulting in an expensive procedure which hasserious risks, side effects, contraindications, and ongoing maintenanceor upgrades. These treatments also have difficulty in targeting andattaching to the specific nerves for the therapy as well as deliveringthe appropriate energy to these nerves. Minimally invasive methods canreduce cost and risk, and improve performance by selectively modulatingthe proper nerves. Delivering the appropriate energy is also essential,as activity can be up-regulated or down-regulated based on theparameters of stimulation. Wirelessly powered devices with communicationcan be desirable because they can be miniaturized and have no need forbattery replacements. However, wireless devices have an even morerestrictive power budget.

Implantable devices that perform various treatments such asneuromodulation treatments are known. Most use large devices withbatteries and long leads to electrically stimulate nerves inside thebody. These devices require invasive implantation, which are verycostly. They also require periodic battery replacement, which requiresadditional surgery. The large sizes of these devices and their highcosts have prevented their use in a variety of applications that havedemonstrated effective neurostimulation treatments.

Nerve stimulation treatments have shown increasing promise recently,showing potential in the treatment of many chronic diseases includingdrug-resistant hypertension, motility disorders in the intestinalsystem, metabolic disorders arising from diabetes and obesity, andchronic pain conditions among others. Many of these treatments have notbeen developed effectively because of the lack of miniaturization andpower efficiency, in addition to other factors. Wirelessly poweredimplantables with communication are desirable because they can beminiaturized and have no need for battery replacements. However,wireless implantables have an even more restrictive power budget.

There have also been several attempts at developing miniature wirelessimplantable, neurostimulators, including the device described in U.S.Pat. No. 5,193,539. This device receives power wirelessly, configuresstimulation, and performs electrical stimulation in a needle injectableform factor. However, the systems in place for power delivery are highlysensitive to placement and alignment, and offer limited bandwidth fordata communications. The receiver operates at MHz frequencies through aninductive link, requiring multiple coils and ferrite cores. Morerecently, new neurostimulation devices have transitioned to operation athigher frequencies, though these devices presently rely on dipoleantennas and struggle with data transfer because of challenges withhigh-frequency operation. Furthermore, these devices provide stimulationfrom directly rectifying the power waveform, reducing the precision ofcontrol and introducing additional complexity and overhead in theoverall system. These systems can also have limitations in the durationof pulses that can be delivered, and long pulses can be necessary toinduce therapeutic effects for many applications, including gastricstimulation. These systems also may rely on instantaneously receivedpower to stimulate excitable tissue and do not aggregate received energyfor use in therapy. Additionally, these systems may not provide for away to use larger non-dipole antennas.

The above described miniaturized neuromodulators can achieveminiaturization in part by relying on external power source to eitherrecharge batteries or energy storage components such as capacitors, orto instantaneously power the implant. Additionally, much of the controlfor proper implant operation is typically located on the controllerwhich is external to the patient body. Therefore, the external systemshould have several important characteristics, such as ability towirelessly supply power to implants, communicate with implants toprogram their operation and receive feedback about therapy and status ofthe implant, interface with the user which could be a doctor whoprograms and monitors the therapy or actual patient. Physically, theexternal system should be comfortable to wear, light weight andportable, have easy and intuitive maintenance and interface. Also, theoverall system should be safe and secure for the patient and compliantwith a variety of regulations while being very robust and versatile toaccommodate a variety of patients, conditions, uses and applications.

There is a need for apparatus form factors that are designed forsimplicity of implantation as well as effective delivery to specificlocations with proper electrical connectivity to tissue. Differentpatients and different treatments have different requirements, and thereis a need to accommodate the needs of different operating conditions.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

SUMMARY

The present inventions relate to neuromodulation methods, systems, andapparatus for the treatment of chronic pain conditions as well as otherconditions or disorders. In particular, embodiments of the inventionprovide for precise, controlled modulation of specific nerves or tissuesto induce physiological effects for therapies. Additionally, methods forincorporating information for diagnostics or improved therapeuticefficacy are described. In the preferred embodiment, the methodsdescribed herein are accomplished with a minimally invasiveneuromodulation system that can target specific nerves with configurablemodulation parameters and/or sensors for diagnostics or adaptations tothe therapy.

The present inventions relate to neuromodulation methods, systems, andapparatus for the treatment of pain management as well as otherconditions or disorders. In particular, embodiments of the inventionprovide for precise, controlled modulation of specific nerves or tissuesto induce physiological effects for therapies. Additionally, embodimentsthat incorporate information for diagnostics or improved therapeuticefficacy are described. Also, systems, apparatus, and devices thatimprove the therapies or the diagnostics are described.

The modulating energy for these therapies may directly or indirectlyeffect the composition or behavior of the targeted nerve or tissue, andspecific parameters will be described in more detail for differenttreatment modalities. This may include placing the modulators in,around, or in the proximity of nerves or tissues to be influenced. Themodulators may be directly or indirectly attached to the nerves througha variety of methods based on the specific type of nerve or tissue aswell as the intended therapy. Close proximity to nerves can reduceenergy requirements and can eliminate unwanted stimulation ofsurrounding nerve tissue. The modulators may be placed at a multitude oflocations and configured with multiple parameters to increase theconfigurability of the treatment. For example, high frequencystimulation can block signals, while low frequency stimulation can masksymptoms. Devices or apparatuses may have specifically designed coatingsto reduce tissue interface impedance, which can in turn reduce the powerrequired for the system, devices, or apparatuses. Multiple nerves can bestimulated in coordination, which may be provided with multiplemodulators or interfaces. Real-time information, which may be providedby sensors in the devices or apparatuses, can further enhance theefficacy of therapy and may be applied for guided placement of aninterface.

The conditions to be treated by the various systems, devices,apparatuses, and methods of the present disclosure include chronic andacute pain. Chronic pain may include but is not limited to lower backpain, migraine headaches, pain associated with herniated discs, musclespasm or pinched nerve anywhere in the body, foot pain such as plantarfascitis, plantar fibroma, neuromas, neuritis, bursitis, and ingrowntoenails. Also addressed may be pain associated with malignant tumors.Acute pain may include but is not limited to post-surgical pain such aspain associated with thoracotomy or inguinal hernia repair, painassociated with procedures where an epidural block is used. This may beparticularly and uniquely applicable in pregnancy to preliminarilydisable the sensory nerves without the use of drugs and prior todelivery to avoid the potential for missing the window of time where anepidural can be administered.

A variety of treatment locations and other pain conditions arecontemplated, including but not limited to the dorsal root ganglion or alocation proximal to the dorsal root ganglion; somatic, afferent,nociceptive, and neuropathic pain; and, diabetic, abdominal, and cancerrelated pain. Systems, devices, and apparatuses of the presentdisclosure may have a diverse feature set to accommodate to the needs ofthe variety of indications.

The methods described also involve the location of placement of themodulating device and its interface with nerves or tissue, the specificnerves or tissues that are being targeted for the therapy, themodalities for modulating the nerves or tissue, and the techniques forattaching the device to the desired sites for the modulation system andits interface. Many of the devices, apparatuses, and tissue interfacesdescribed herein may be delivered in a minimally invasive manner throughan introducer with anatomical guidance. The delivery of the interfacesmay be simple and minimally invasive and the interfaces may be deliveredin conjunction with the wireless devices of the system.

The apparatus and systems described herein include electrodes,connectors, anchors, and other devices and materials that allow forimproved therapies or diagnostics. In some cases, the apparatuses andsystems may be configured to be powered wirelessly, transmit datawirelessly, have energy storage, and/or have local generation of themodulation, thereby providing miniaturized devices capable of precisetherapies and feedback systems. In some cases, the devices described arespecially designed for specific locations or nerves inside the body.Anatomical considerations for each application can be important forimplantation procedures and the location site of any implantable device,and can dramatically influence efficacy of the implantable device. Thesystems and apparatuses for different anatomical sites associated withthe therapies may include at least one specific attachment device thatthese interfaces can accommodate.

The present inventions relate to methods of making and using a system orapparatus for minimally invasive neuromodulation devices with sensingcapabilities and versatility for operation with a wide variety ofapplications, and to the external system which powers such implants,controls their operation, gathers information from them, provides aninterface for a patient and a doctor to control the therapy and monitorits effectiveness. These implantable devices are versatile and can beimplanted in a variety of organs and body areas to treat a variety ofconditions and diseases. The external system, which may include one ormore of the external devices, therefore, may have different embodimentsfor all these various applications. However, the core components andfunctionality of the external system which are critical to the operationof versatile minimally invasive neuromodulators are described in thisinvention.

According to one aspect of the present inventive concepts, a stimulationor diagnostic system comprises an external device (such as a patch)configured to transmit and/or receive wireless transcutaneoustransmissions, and at least one implantable device or implant configuredto receive wireless transcutaneous transmissions from the at least oneexternal device and/or to transmit wireless transcutaneous transmissionsto the at least one external device.

In some embodiments, the implantable device comprises a stimulator forneuromodulation of tissue.

In some embodiments, the implantable device includes one or moreindependently controlled electrodes.

In some embodiments, the wireless transmissions operate in one or moreof the industrial, scientific, and medical (ISM) radio bands.

In some embodiments, the implantable device comprises one or more of:pulse generator; extension; leads; patient programmer.

In some embodiments, the system or apparatus is configured to adhere toANSI standards for spinal cord stimulators.

In some embodiments, the implantable device comprises a therapeuticelement.

In some embodiments, the system or apparatus further comprises apositioning algorithm configured to position the at least one externalpatch device relative to the at least one implantable device. Betterlinks between the external device(s) and the implantable device(s) candramatically increase system efficiency, which can increase battery lifeand reliability. In some embodiments, the positioning algorithm canposition the at least one external device relative to multipleimplantable devices. In multi-component or multi-device systems such asthese, positioning can be important to ensure that each individualcomponent or device is receiving sufficient power. In some embodiments,the positioning algorithm can be configured to optimize link gain. Insome embodiments, the positioning algorithm can be configured tomaximize the average rate of charge among the implantable devices. Insome embodiments, the positioning algorithm can be configured tomaximize the minimum received power among the implantable devices. Insome embodiments, the positioning algorithm can be configured tomaximize a weighted rate of charge for the implantable devices. In someembodiments, the positioning algorithm comprises a gradient searchalgorithm. In some embodiments, the system or apparatus is configured totake a measurement while transmitting power at a higher than averagepower level. In some embodiments, the system or apparatus can beconfigured to optimize one or more of: antenna position; EM focusingsuch as beam steering and/or midfield focusing; electrical lensadjustment such as an adjustment caused by phase change materials oradjust to focus and/or beam steer in tissue; antenna reconfiguration,such as through segmentation, to modify antenna geometry; control ofenabled antennas; control in phase and amplitude of signal transmittedfrom one or more antennas. Midfield powering or focusing, for example,can allow multiple devices to be powered and communicated with through ahigh bandwidth channel. External control devices and the communicationprotocols they use may allow for independent control of the functionalcomponents on the implant while minimizing disturbances in powertransfer.

In some embodiments, the at least one external device is configured toadjustably control power transfer from the at least one external patchto the at least one implantable device. In some embodiments, the controlof power transfer comprises closed loop power transfer. The preciseamount of necessary power can be delivered, ensuring that the system canoperate with maximum efficiency. Power usage and management can beoptimized over multi-component or multi-device systems, delivering powerpreferentially to components or devices that require more power. In someembodiments, the at least one implantable device further comprises apower supply, and the power transfer is configured based on the chargeand/or discharge rate of the at least one implantable device powersupply. In some embodiments, the adjustable control of power transfercomprises an adjustment to a parameter selected from the groupconsisting of: transmitted power level; frequency; envelope of thetransmitted carrier; duty cycle; number of carriers transmitted andtheir parameters; and combinations thereof. In some embodiments, theadjustable control of power transfer comprises adjusting a matchingnetwork parameter. In some embodiments, the adjustable control of poweris performed by sensing a reflection coefficient and/or standing waveson the at least one external device. In some embodiments, the at leastone external device is configured to deliver a first wirelesstransmission at a first frequency and a second wireless transmission ata second frequency, wherein the system or apparatus is configured tocompare the first wireless transmission to the second wirelesstransmission. In some embodiments, the comparison of performance atdifferent frequencies comprises a comparison of power transferred ateach frequency. In some embodiments, the comparison of performance atdifferent frequencies comprises a comparison of data transferred at eachfrequency. In some embodiments, the system or apparatus is furtherconfigured to select the first frequency or the second frequency tosatisfy a minimum power requirement of the at least one implantabledevice. In some embodiments, the at least one implantable devicecomprises multiple implantable devices, wherein the at least oneexternal device is configured to adjustably control power transfer fromthe at least one external device to the multiple implantable devices. Inthe some embodiments, the at least one external patch device isconfigured to increase the power delivered to a first implantable deviceas compared to a second implantable device. In some embodiments, thefirst implantable device is receiving less power than the secondimplantable device. In some embodiments, the first implantable devicecomprises a higher power requirement than the second implantable device.

In some embodiments, the at least one external device and the at leastone implantable device comprise a matching network, wherein the systemor apparatus is configured to determine a mismatch in the impedances anddetermine desired adjustments to the at least one external device and/orthe at least one implantable device matching networks. Impedancemismatching can result in efficiency losses of 50% or more, and antennaimpedances can vary with the environment, particularly the external.Adjustable impedance matching can minimize losses and allow foradaptations from patient to patient and over time. In some embodiments,the system or apparatus is configured to determine the mismatch bymonitoring reflected power, wherein the system or apparatus comprisesmultiple matching network elements, and wherein the adjustment comprisesa selection of one or more of the multiple matching network elementsthat reduce the mismatch. In some embodiments, the at least one externaldevice comprises an antenna and/or antenna circuitry, and wherein thesystem or apparatus is configured to monitor the temperature of theantenna and/or antenna circuity and detect a mismatch, improperoperation, and/or failure when the temperature level exceeds athreshold.

In some embodiments, the overall system further comprises a handheldinterface configured to transmit and/or receive transmissions to and/orfrom the at least one external device. In some embodiments, thetransmissions transmitted and/or received by the handheld devicecomprise wireless transmissions. In some embodiments, the transmissionstransmitted and/or received by the handheld device comprise wiredtransmissions. In some embodiments, the transmitted and/or receivedtransmissions comprise a protocol and/or standard selected from thegroup consisting of: Bluetooth; WiFi, ZigBee; Qualcomm 2net; MICS; ISM;WMTS; MedRadio; MNN; MBAN; cellular communications; RFID communications;and combinations thereof. In some embodiments, the handheld interface isfurther configured to transmit and/or receive wireless transmissions toand/or from the at least one implantable device.

In some embodiments, the system or apparatus further comprises a userinterface configured to provide information to a user. In someembodiments, the user interface may provide real-time feedback of theoperation of the implantable system of device(s). In some embodiments,the user interface simplifies device usage and can take severaluser-friendly form factors, which can allow for more convenient devices.In some embodiments, the user comprises a user selected from the groupconsisting of: clinician; patient; caregiver; family member; andcombinations thereof. In some embodiments, the provided informationcomprises information selected from the group consisting of: stimulationparameters; energy transmission parameters such as energy transmissionpower level; power supply level; information transmission parameterssuch as information transmission power level; stimulation historyinformation; patient compliance information; schedule of futurestimulation; sensor information; alarm and alert information; andcombinations thereof. In some embodiments, the provided informationcomprises information selected from the group consisting of: treatmentdelivered over time; delivered energy; therapy parameters; visualizationof sensed activity in tissue; an operating parameter of the at least oneimplantable device; an operating parameter of the at least one externalpatch device; and combinations thereof. In some embodiments, the systemor apparatus further comprises a user input device configured to allow auser to change a system or an apparatus parameter. The feedbackinformation can allow doctors or patients to make informed changes tothe system operation and can allow for sophisticated monitoring of thetherapy. In some embodiments, the user input device comprises a deviceselected from the group consisting of: touchscreen; controllable cursor;mouse; keyboard, switch; and combinations thereof. In some embodiments,the system or apparatus parameter to be changed comprises a parameterselected from the group consisting of: stimulation parameters of one ormore implants; transmitted power parameter; antenna position; nerveinterface configuration; and combinations thereof. In some embodiments,the at least one external device comprises multiple external devices,such as multiple external patches, wherein the at least one implantabledevice comprises multiple implantable devices; and wherein each externaldevice communicates with at least one implantable device. In someembodiments, the multiple external devices and the multiple implantabledevices are configured as a network to coordinate therapeutic and/ordiagnostic information. In some embodiments, the system or apparatusfurther comprises a master clock configured to synchronize the multipleexternal patch devices. In some embodiments, the multiple implantabledevices are synchronized. In some embodiments, the system or apparatusfurther comprises a master clock, wherein each external device comprisesa local clock which is phase and/or frequency synchronized to the masterclock. In some embodiments, the multiple external devices aresynchronized, wherein calibration of the system or apparatus parametersaccomplished by operating the multiple external devices in asynchronized manner.

In some embodiments, the at least one external device further comprisesan electronic component selected from the group consisting of: sensor;power supply; transmitter; receiver; signal conditioner; multiplexor;controller; memory; user interface; tissue interface; and combinationsthereof.

In some embodiments, the at least one external device further comprisesan attachable battery.

In some embodiments, the at least one external device comprises arechargeable battery. In some embodiments, the rechargeable batterycomprises an attachable rechargeable battery. In some embodiments, thesystem or apparatus further comprises a charging device configured tocharge the rechargeable battery. In some embodiments, the chargingdevice is configured to wirelessly transfer power to the rechargeablebattery. In some embodiments, the charging device can comprise aninductive and/or mid-field coupling link and/or far-field linkconfigured to transfer power to the rechargeable battery. In someembodiments, the charging device comprises a first coil and a firstmating portion, and the at least one external device comprises a secondcoil and a second mating portion constructed and arranged to align thefirst coil with the second coil during charging. In some embodiments,the first mating portion comprises at least one of a projection or arecess and the second mating portion comprises a mating recess orprojection. In some embodiments, the first mating portion comprises atleast one of a magnet or magnetic material and the second mating portioncomprises a mating magnetic material or magnet. In some embodiments, thefirst mating portion comprises a magnet and the second mating portioncomprises a magnet. In some embodiments, the charging device isconfigured as a bed-side monitor.

In some embodiments, the at least one external device or patch comprisesa flexible substrate configured to attach the at least one externaldevice to the patient. In some embodiments, the at least one externalpatch device further comprises skin contacts attached to the flexiblesubstrate. In some embodiments, the at least one external patch devicefurther comprise an adhesive layer. In some embodiments, the adhesivelayer comprises impedance matching gels and/or hydrogels. In someembodiments, the at least one external patch device further comprisesone or more electronic components selected from the group consisting of:sensor; power supply; transmitter; receiver; signal conditioner;multiplexor; controller; memory; antenna; and combinations thereof. Insome embodiments, the one or more electronic components are positionedon and/or within the substrate. In some embodiments, the at least oneexternal patch device can further comprise an antenna. In someembodiments, the at least one external patch device further comprises acable attaching the one or more of the electronic components to theantenna. In some embodiments, the cable comprises one or more portionsthat are rigid, semi-rigid or flexible. In some embodiments, the cablecomprises an e-textile cable, and/or antenna. In some embodiments, theat least one external patch device further comprises a power supply. Insome embodiments, the power supply comprises a component selected fromthe group consisting of: battery; attachable power supply; multipleattachable power supplies; rechargeable power supply; wirelesslyrechargeable power supply; and combinations thereof. In someembodiments, the at least one external patch device further comprises anantenna and gel, wherein the gel is configured to improve performance ofantenna, tissue contacts (electrodes), heat removal; reduction ofirritation; etc. In some embodiments, the gel comprises a gel selectedfrom the group consisting of: contact gels; matching gels; andcombinations thereof. The external patch device(s) may come in multipleform factors, including necessary electronics, rechargeable batteries,flexible substrates, garments, and multiple antenna arrays. The externalpatch device(s) may provide a comfortable system that can be flexiblydesigned based on patient feedback and usability testing. Rechargeable,replaceable batteries can simplify the recharging protocols for theexternal patch device(s).

In some embodiments, the at least one external device further comprisesat least one antenna. The external device(s) may comprise multipleantennas or distributed antennas in different locations around the bodyof the patient. The external device(s) may form a network and mayperform coordinated therapies with implants distributed in differentlocations around the body. The external device(s) may coordinate withone another based on sensed information and alter their operation asnecessary. The configurations of the antennas may be sophisticated so asto desensitize placement and alignment, and to focus energy to improvepower transfer. In some embodiments, the at least one antenna comprisesa positionable antenna. In some embodiments, the at least one antennacomprises an adjustable antenna. In some embodiments, the adjustableantenna comprises an electrical lens. In some embodiments, theadjustable antenna comprises energy focusing antenna. In someembodiments, the energy focusing is configured to maximize electric ormagnetic field distribution at a particular location inside tissue tolocalize energy delivery to one or more implantable devices. In someembodiments, the energy focusing utilizes midfield wireless powering. Insome embodiments, the energy focusing utilizes nearfield wirelesspowering. In some embodiments, the energy focusing utilizes far-fieldwireless powering. In some embodiments, the energy focusing isreconfigurable or adjustable. In some embodiments, the adjustableantenna comprises a self-adjusting antenna. In some embodiments, the atleast one external device comprises a ferrite core, wherein the at leastone implantable device comprises a magnet, and wherein the adjustableantenna self-adjusts through magnetic alignment of the ferrite core andmagnet. In some embodiments, the self-adjusting antenna is electricallysteered. In some embodiments, the self-adjusting antenna comprises anarray of antennas each configured for phase adjustment to accomplishbeam steering and/or beam focusing. In some embodiments, the system orapparatus further comprises a patient worn device, wherein the at leastone antenna is embedded in the patient worn device. In some embodiments,the patient worn device comprises a device selected from the groupconsisting of: shirt; belt; cloth band; hat; and other wearable items;and combinations thereof. In some embodiments, the at least one antennacomprises multiple antennas. In some embodiments, the system orapparatus further comprises an algorithm configured to coordinateactivation of one or more antennas to optimize delivery of power to theat least one implantable device. In some embodiments, the algorithm isconfigured to activate the one or more antennas based on couplingefficiency with the at least one implantable device. In someembodiments, the activation results in a focusing effect and/or a beamsteering effect. In some embodiments, the at least one antenna comprisesmultiple selectable conducting elements. In some embodiments, one ormore of the selectable conducting elements are selected to optimizecoupling with the at least one implantable device. In some embodiments,the system or apparatus further comprises a separator between the atleast one antenna and tissue of the patient. In some embodiments, theseparator comprises an element selected from the group consisting of:air; soft pad; gel; matching gel; contact gel; thermal insulator; fluid;recirculating fluid; and combinations thereof. In some embodiments, theseparator is constructed and arranged to improve performance of the atleast one antenna. In some embodiments, the separator is constructed andarranged to insulate the patient tissue from heat generated by the atleast one external patch device. In some embodiments, the separator isconstructed and arranged to maintain constant relative position withrespect to tissue and at least one implantable device. In someembodiments, the separator is constructed and arranged to remove excessheating from tissue.

In some embodiments, the system or apparatus further comprises at leastone body electrode configured to be positioned on the patient's skin andto produce a signal to be transmitted to the at least one device. Thebody electrode(s) can provide a potential alternative communication pathfor information between the implant(s) and the external patch device(s)or device (s). The body electrode(s) can monitor the stimulation therapyor other patient parameters during the operation of the device, ensuringthe proper functioning of the device. The body electrode(s) can providestochastic resonance, which can prime the nerves for stimulation,reducing the required energy for therapy. In some embodiments, the atleast one body electrode comprises a component selected from the groupconsisting of: volume conduction electrodes; EKG-type contact electrode;hydrogel; adhesive; and combinations thereof. In some embodiments, theat least one body electrode comprises multiple body electrodes. In someembodiments, the at least one body electrode comprises an attachmentelement. In some embodiments, the attachment element comprises anelement selected from the group consisting of: adhesive; conductiveadhesive; gel; hydrogel; conductive gel; short-wear gel; extended-weargel; and combinations thereof. In some embodiments, the attachmentelement comprises a conductive material whose impedance is configured tominimize reflections at an interface with the patient's skin. In someembodiments, the at least one body electrode is further configured toreceive data from the at least one implantable device. In someembodiments, the at least one body electrode is configured to senseand/or monitor the therapy delivered by the implantable device. In someembodiments, the data is received via body conduction communication. Insome embodiments, the at least one implantable device is configured tosend data to the at least one body electrode by modulating itsstimulation signal. In some embodiments, the at least one implantabledevice is configured to modulate the voltage and/or current of itsstimulation signal. In some embodiments, the at least one implantabledevice is configured to modulate the stimulation signal withoutinterfering with the therapy delivered by the stimulation signal. Insome embodiments, the system or apparatus is configured to adjust the atleast one implantable device based on the body electrode receivedsignal. In some embodiments, the adjustment to the at least oneimplantable device comprises an adjustment to one or more of: voltage;current; frequency; duty cycle; pulse shape; duration of therapy and/orstart and stop times of therapy. In some embodiments, the adjustment tothe at least one implantable device comprises a calibration of one ormore of: the at least one external patch device; the at least oneimplantable device; and/or the coupling between the at least oneexternal device and the at least one implantable device. In someembodiments, the system or apparatus is configured to adjust the atleast one implantable device to compensate for an event selected fromthe group consisting of: patient physical activity; electrode migration;tissue interface impedance; a time-varying parameter affectingtherapeutic outcome; and combinations thereof. In some embodiments, thesystem or apparatus is configured to locate the at least one implantabledevice using the body electrode received and/or produced signal. In someembodiments, the system or apparatus is configured to locate the atleast one implantable device using multiple stimulation signalscomprising different stimulation parameters. In some embodiments, thesystem or apparatus is configured to locate the depth and/or position intissue of the at least one implantable device. In some embodiments, theat least one body electrode is further configured to deliver energy totissue and/or the at least one implantable device. In some embodiments,the delivered energy is configured to perform a function selected fromthe group consisting of: communicate with the at least one implantabledevice; modulate tissue; improve therapy produced by the at least oneimplantable device by reducing the activation threshold of excitabletissue; block neural activity; stimulate neural activity; improveefficiency of the at least one implantable device and/or the system orapparatus; interact with one or more sensors; improve therapeuticoutcomes; inhibit and/or promote one or more nerve activationthresholds; and combinations thereof.

In some embodiments, the at least one implantable device comprisesmultiple implantable device.

In some embodiments, the at least one implantable device comprises anenergy storage element.

In some embodiments, the at least one implantable device comprises anintegrated circuit assembly comprising one or more elements selectedfrom the group consisting of: power management circuitry; implantcontroller circuitry; sensor interface circuitry; sensor; transmitter;receiver; pulse generator circuitry; electrode; electrode drivecircuitry; energy storage element; matching network; kill switch; uniqueidentification storing circuitry and/or elements; power-on-resetcircuit; bandgap reference circuit; calibration circuit; timing circuit;antenna; charge balance circuit; safety and failure prevention anddetection circuits; overvoltage protection circuit; overcurrentprotection circuit; interference detection circuit; chip auxiliarycircuitry; and combinations thereof. Implantable device s should be safeand reliable and fail-safe protocols can ensure that the devices do notharm the patient. Monitoring of the patient and the implantable devicecan ensure that it functions as detected and can allow for immediatedetection of malfunctions.

In some embodiments, the at least one implantable device comprises atleast one antenna. In some embodiments, the at least one antennacomprises a positionable antenna. In some embodiments, the at least oneantenna comprises an adjustable antenna. In some embodiments, theadjustable antenna comprises an electrical lens. In some embodiments,the adjustable antenna comprises a self-adjusting antenna. In someembodiments, the at least one external patch device comprises a ferritecore, wherein the at least one implantable device comprises a magnet,and wherein the adjustable antenna self-adjusts through magneticalignment of the ferrite core and magnet. In some embodiments, theself-adjusting antenna is electrically steered. In some embodiments, theself-adjusting antenna comprises an array of antennas each configuredfor phase adjustment to accomplish beam steering and/or beam focusing.In some embodiments, the at least one antenna comprises multipleantennas. In some embodiments, the system or apparatus further comprisesan algorithm configured to coordinate activation of one or more antennasto optimize delivery of power to the at least one implantable device. Insome embodiments, the algorithm is configured to activate the one ormore antennas based on coupling efficiency with the at least oneimplantable device. In some embodiments, the activation results in afocusing effect and/or a beam steering effect. In some embodiments, theat least one antenna comprises multiple selectable conducting elements.In some embodiments, one or more of the selectable conducting elementsare selected to optimize coupling with the at least one implantabledevice. One or more implantable device configurations with midfieldwireless transmissions and techniques for optimizing the antenna linkmay be provided. Multi-device systems may introduce complexity in thefunctionality of the overall system and may require an intelligentsystem to operate effectively. The antenna sub-systems may define thepower budget of the overall system, and improvements in the link mayresult in better usability with increased reliability.

In some embodiments, the wireless transcutaneous transmissions receivedby the at least one implantable device comprise both data and power.

In some embodiments, the wireless transcutaneous transmissions receivedby the at least one implantable device comprise at a distance smallerthan one hundredth of the wavelength.

In some embodiments, the wireless transcutaneous transmissions receivedby the at least one implantable device operate at a distance within 100×the size of a wavelength.

In some embodiments, the wireless transcutaneous transmissions receivedby the at least one implantable device operate at a distance greaterthan 100× the size of a wavelength.

In some embodiments, the wireless transcutaneous transmissionstransmitted by the at least one implantable device comprises data. Insome embodiments, the data is related to the status of the at least oneimplantable device on state. In some embodiments, the data is related toa POR triggered signal. In some embodiments, the data is related to therate of charge of the at least one implantable device.

In some embodiments, the system or apparatus further comprises a sensor.In some embodiments, the sensor comprises multiple sensors. In someembodiments, the sensor comprises a temperature sensor configured toproduce a temperature signal. In some embodiments, the system orapparatus is configured to prevent tissue of the patient from exceedinga threshold based on the temperature signal. In some embodiments, thetemperature sensor comprises a sensor selected from the group consistingof: thermocouple; temperature dependent resistor (thermistor); infraredsensor; semiconductor; thermopile; and combinations thereof. In someembodiments, the system or apparatus further comprises a recirculatingfluid supply configured to cool tissue based on the temperature signal.In some embodiments, the system or apparatus is configured to adjustenergy delivered by the at least one external device based on thetemperature signal.

In some embodiments, the system or apparatus further comprises a faultassembly configured to prevent and/or detect a fault in the system orapparatus. In some embodiments, the fault assembly is positioned in alocation selected from the group consisting of: the at least oneexternal device; the at least one implantable device; and combinationsthereof. In some embodiments, the fault assembly is configured to detectimproper relative positioning between the at least one external deviceand the at least one device. In some embodiments, the fault assemblycomprises electronic circuitry configured to perform a function selectedfrom the group consisting of: overcurrent protection; overvoltageprotection; charge imbalance detection; short circuit protection;heating detection; unauthorized programming detection; detection of lossin link; electrode-tissue interface impedance malfunction detection;circuit miscalibration and/or malfunction detection; detection and/orcorrection of errors in data; and combinations thereof. In someembodiments, the fault assembly is configured to detect an inadequatepower link and/or an inadequate data link. In some embodiments, thefault assembly is configured to detect an inadequate data link using amethod selected from the group consisting of: repetition codes; paritybits; checksums; cyclic redundancy checks (CRC); cryptographic hashfunctions; error-correcting codes; automatic repeat requests; andcombinations thereof. In some embodiments, the fault assembly isconfigured to detect improper program settings. In some embodiments, thefault assembly is configured to detect potentially harmful environmentfor the implantable device selected from a group of: electric field;magnetic field, such as during MRI; radiation; interference; andcombinations thereof. In some embodiments, the fault assembly isconfigured to disable system or apparatus operation upon detection of afault condition. In some embodiments, the fault assembly comprisesnon-volatile memory. In some embodiments, the fault assembly isconfigured to prevent adverse events resulting from environmentalelectromagnetic fields. In some embodiments, the fault assembly isconfigured to temporarily disable system or apparatus operation. In someembodiments, the fault assembly comprises a remotely controllable switchconfigured to allow programming via a method selected from a group of:magnetic field; magnetic field gradient; electric field; electric fieldgradient; and combinations thereof. In some embodiments, the switchcomprises a magnetic switch. In some embodiments, the at least oneimplantable device is configured to communicate the fault condition tothe at least one external patch device. In some embodiments, thecommunication method can be selected from a group of: electromagneticsignal; body conduction signal; sound signal; optical signal; mechanicalsignal, such as vibration and/or rotation or movement; and combinationsthereof. In some embodiments, the system or apparatus further comprisesa handheld device comprising a display, wherein the system or apparatusis configured to present the fault condition on the handheld devicedisplay. In some embodiments, the fault assembly is configured tomonitor one or more of: antenna radiation; energy reflections; datatransmission; data reception; tissue temperature; and/or SAR.

In some embodiments, the at least one implantable device is implantablein (e.g., within, on and/or proximate) one or more of the followingsites: the tibial nerve (and/or sensory fibers that lead to the tibialnerve); the occipital nerve; the sphenopalatine ganglion; the sacraland/or pudendal nerve; target sites in the brain, such as the thalamus;the vagus nerve; baroreceptors in a blood vessel wall, such as in thecarotid artery; along, in, or proximal to the spinal cord; one or moremuscles; the medial nerve; the hypoglossal nerve and/or one or moremuscles of the tongue; cardiac tissue; the anal sphincter; peripheralnerves of the spinal cord, including locations around the back; thedorsal root ganglion; and motor nerves and/or muscles. The flexibilityof the devices and systems described herein can allow for a variety oftherapies throughout the body.

In some embodiments, the system or apparatus is configured to stimulateone or more of: tibial nerve (and/or sensory fibers that lead to thetibial nerve); the occipital nerve; the sphenopalatine ganglion; thesacral and/or pudendal nerve; target sites in the brain, such as thethalamus; the vagus nerve; baroreceptors in a blood vessel wall; thespinal cord; one or more muscles; the medial nerve; the hypoglossalnerve and/or one or more muscles of the tongue; cardiac tissue; the analsphincter; peripheral nerves of the spinal cord; the dorsal rootganglion; and motor nerves and/or muscles.

In some embodiments, the overall system is configured to stimulate totreat one or more of: migraine; cluster headaches; urge incontinence;tremor; obsessive compulsive disorder; depression; epilepsy;inflammation; tinnitus; high blood pressure; pain; muscle pain; carpaltunnel syndrome; obstructive sleep apnea; cardiac arrhythmia or othercardiac disease or disorder that could benefit from pacing ordefibrillation; dystonia; interstitial cystitis; gastroparesis; obesity;fecal incontinence; bowel disorders; chronic pain; and/or compromisedmobility.

The present inventions relate to methods of making and using a system oran apparatus for powering, controlling, and receiving information fromminimally invasive devices, which have the capability of activation andsuppression of tissue or cellular activity and/or sensing withversatility for operation with a wide variety of applications. Theimplantable devices are versatile in their applications and are highlyconfigurable to accommodate a variety of therapies and potentiallydiagnoses. Alternatively or additionally, the external system can alsobe versatile, can have the ability to wirelessly power these implants,can have high data rate communications to be able to control and receiveinformation from one or more implants, can have an intuitive userinterface for a doctor, or other user, can provide feedback andrecommendations for users, can monitor therapy progress and update thepatient and/or doctor of its efficacy and safety and the status of oneor more implants. The external system of device(s) can also becomfortable for short term, prolonged term, and potentially chronic use.The present invention will, therefore, address these importantconsiderations and describe an embodiment which encompasses theseimportant features.

The present inventions relate to systems or apparatuses for treating apatient, such as systems or apparatuses for neuromodulating nerve orother tissue for treating pain and/or other patient diseases anddisorders.

According to aspects of the present disclosure, an overall system for apatient comprises at least one external system of device(s) configuredto transmit and receive wireless transcutaneous transmissions and atleast one implanted system of device(s) configured to be implanted inthe patient and receive wireless transcutaneous transmissions from theat least one external device and/or to transmit wireless transcutaneoustransmissions to the at least one external device.

In some embodiments, the overall system comprises a stimulationapparatus configured for the neuromodulation of tissue.

In some embodiments, the overall system comprises a stimulationapparatus configured for the treatment of pain.

In some embodiments, the at least one implantable system comprisesmultiple discrete components and/or the at least one external systemcomprises multiple discrete components, and the multiple discretecomponents are configured as a network of components.

In some embodiments, the overall system is configured to transmit powerand data between the at least one implantable system and the at leastone external system.

In some embodiments, the at least one implantable system comprisesmultiple discrete components each comprising a sealed enclosure. Theimplantable system can be configured to transfer data to the multiplediscrete components simultaneously. The sealed enclosures can compriseglass.

In some embodiments, the at least one implantable device of theimplantable system comprises one or more components selected from thegroup consisting of: one or more antennas; one or more electrodes;energy harvesting circuit; energy management circuit; one or more energystorage elements; pulse generator; controller, stimulation currentdriver; one or more sensors; communications circuits for receiving andsending data; calibration circuits; startup and power-on-reset circuits;memory circuits; timing circuits; other auxiliary circuits, such as amatching network, that are necessary for proper implantable systemoperation and a particular application; and combinations thereof.

In some embodiments, the at least one implantable device of theimplantable system comprises at least one electrode configured toindependently deliver energy to tissue. The at least one electrode cancomprise a paddle electrode. The at least one electrode can comprise ananchorable electrode. The at least one electrode can comprise a coating.The coating can comprise platinum, iridium, gold, alloys, carbonnanotubes, or combinations thereof. The electrode can comprise amicroelectrode. The microelectrode can protrude from the enclosure orthe lead. The at least one electrode can be constructed and/or arrangedto stimulate the dorsal root ganglion. The at least one electrode cancomprise multiple electrodes. The multiple electrodes can be placed10-50 cm apart across the patient's back or torso. The multipleelectrodes can be placed in a pattern across the patient's back, whereinthe pattern is selected from the group consisting of: square;rectangular; diamond; circular; elliptical; regular; irregular pattern;and combinations thereof. The multiple electrodes can be implanted toprovide cross-talk. The multiple electrodes can be implanted to steercurrent from one electrode to a second electrode. The multipleelectrodes can each generate voltage or current in reference to a commonreference node. The multiple electrodes can be positioned on themultiple leads. The multiple leads can comprise bifurcated leads. Themultiple leads can be electrically connected in series. The multipleleads can each have a unique addressable ID. The implantable system cancomprise an implantable connector assembly including multiple connectorsand a plug, wherein the plug is configured to seal unused connectors.The multiple electrodes can be positioned on an active lead configuredto send and/or receive commands to and/or from a portion of the at leastone implantable lead. The implantable system can comprise a serialcommunication protocol for sending and/or receiving information. The atleast one electrode can be implanted at a location in proximity totissue to be stimulated. The at least one electrode can be implanted ata location at least partially surrounding the tissue to be stimulated.

In some embodiments, the at least one implantable device of theimplantable system comprises at least one antenna. The at least oneimplantable system can comprise an implantable enclosure, and whereinthe at least one antenna is tethered to the implantable enclosure. Theat least one antenna can be implanted closer to the skin surface thanthe implantable enclosure is implanted. The at least one antenna cancomprise multiple antennas connected to the implantable enclosure by aconnecting element comprising one or more of: connecting interface;cable; wires; conductive lead; transmission line; waveguide; distributedmatching network; transformer; lumped matching network; and combinationsthereof. The connecting element can be configured as a matching network.The connecting element can comprise at least a flexible portion. Themultiple antennas can be implanted at locations to optimize link gain.The multiple antennas can be implanted at locations to decreasesensitivity to position, orientation and/or rotation of one or moreexternal system components. The multiple antennas can comprise at leasttwo antennas configured to be implanted orthogonal to each other. The atleast two antennas can be implanted to minimize sensitivity to theposition of one or more external system components. The multipleantennas can be configured as an antenna selected from the groupconsisting of: loop antenna; multi-loop antenna; orthogonal antennas;polarized antenna structures; dipole antenna; multi-coil antenna;helical antenna; patch antenna; and combinations thereof. The at leastone antenna can comprise a foldable and unfoldable antenna. The antennacan comprise an impedance that matches and/or is resonant with at leasta portion of the at least one implantable system. The antenna can beconfigured as an interposer matching network. The implantable system cancomprise multiple components with different characteristics. The atleast one implantable device of the implantable system can comprise anenclosure, and the antenna can comprise an electrical connectorconfigured to electrically attach to the enclosure.

In some embodiments, the at least one implantable device of theimplantable system comprises a controller and an on-board powermanagement assembly, wherein the controller is configured to control thepower management assembly.

In some embodiments, the at least one implantable device of theimplantable system comprises a pulse generator configured to producecustom stimulation waveforms. The pulse generator can be configured tooperatively adjust a stimulation parameter selected from the groupconsisting of: amplitude; timing; frequency; pulse duration; duty cycle;polarity; and combinations thereof.

In some embodiments, the implantable system is constructed and arrangedto be delivered through a component selected from the group consistingof: needle; endoscope; laparoscope; and combinations thereof.

In some embodiments, the implantable device(s) of the implantable systemcomprises a lead comprising at least one electrode. The lead further cancomprise a cross section with a geometry selected from the groupconsisting of: circular, oval, rectangular; and combinations thereof.The lead further can comprise one or more electronic components and anouter surface surrounding the one or more electronic components. Thelead further can comprise one or more antennas and an outer surfacesurrounding the one or more antennas. The one or more antennas cancomprise multiple antennas distributed along the length of the lead toincrease its radar cross section. The lead further can comprise aproximal end and a housing positioned on the proximal end. The housingcan comprise a sealed housing. The housing can comprise one or more feedthrough configured for: AC coupled channels, such as RF inputs for anantenna; stimulation channels; and/or sensors. The housing can comprisea shape selected from the group consisting of: cylindrical; rectangular;elliptical; spherical; an irregular shape; and combinations thereof. Thesystem or apparatus can further comprise a delivery needle assembly forimplanting the lead. The delivery needle assembly can comprise a firstportion and a second portion, wherein the first portion is configured todetach from the second portion after placement of the lead into thepatient. The delivery needle assembly can comprise a coveringsurrounding a needle, wherein the covering is configured to be cut suchthat the needle can be removed from the lead. The delivery needleassembly can comprise a needle comprising the first portion and thesecond portion, and a hinge rotatably attaching the first portion to thesecond portion such that the needle can be removed from the lead. Thehousing can comprise a connector electrically attached to the at leastone electrode. The lead further can comprise a proximal end and aconnector positioned on the proximal end. The connector can comprise aconnector configured to seal with a mating connector. The at least oneimplantable device can comprise an enclosure comprising the matingconnector. The connector can be configured to attach to an accessorycomponent selected from the group consisting of: lead splitter; activelead interface; passive lead interface; serializer; deserializer; leadextension; lead diagnostic interface; charge balance device; pulseconversion device; pulse shaping device; DC to pulse burst pulse shapingdevice; a filter; an AC coupling capacitor assembly for chargebalancing; and combinations thereof. The implantable device can furthercomprise an active and/or passive distribution circuit configured tooperably attach to the lead. The lead further can comprise at least onelumen. The implantable device can further comprise a filament slidinglyreceived by the lumen and configured to aid in implantation of the lead.The filament can be constructed and arranged to adjust the stiffness ofthe lead. The filament can comprise a curved distal portion. The lumencan comprise a cross section with a geometry selected from the groupconsisting of: circular, oval, rectangular; and combinations thereof.The lead further can comprise a sensor. The sensor can be constructedand arranged to produce a signal corresponding to a parameter selectedfrom the group consisting of: action potential; neural activity; muscleactivity; pressure; temperature; pH; and combinations thereof. The leadcan comprise a first lead and the at least one implantable devicecomprises a second lead and an implantable enclosure, wherein the firstlead and the second lead are each configured to operably attach to theenclosure. The first lead and the second lead can comprise a differentproperty selected from the group consisting of: length; diameter;electrode shapes; electrode sizes; electrode configurations; andcombinations thereof. The lead further can comprise an antenna. Theantenna can comprise an elongated antenna. The elongated antenna cancomprise an antenna selected from the group consisting of: dipoleantenna; elongated loop antenna; elongated multi-loop antenna; andcombinations thereof. The lead further can comprise a flexible PCBoperably connected to the at least one electrode.

In some embodiments, the at least one implantable device of theimplantable system comprises at least a portion with a controllablestiffness and/or shape. The at least a portion can comprise a shapedmemory alloy.

In some embodiments, further comprising a sheath, the at least oneimplantable device comprises a portion surrounded by the sheath. Thesheath can be stiffer than the surrounded portion of the at least oneimplantable device. The sheath can comprise a biased portion. The sheathcan be constructed and arranged to provide support for a componentselected from the group consisting of: camera; fiber; visible lightfiber; ultrasound fiber; a sensing lead; a tool; implantable device; atleast one portion of implantable device; and combinations thereof. Thesheath can comprise a sensor. The sensor can be constructed and arrangedto produce a signal corresponding to a parameter selected from the groupconsisting of: action potential; neural activity; muscle activity;pressure; temperature; pH; and combinations thereof.

In some embodiments, the at least one implantable device comprises atleast four stimulation channels. The at least one implantable device cancomprise at least eight stimulation channels.

In some embodiments, the at least one implantable device comprises an ACcoupled interface. The AC coupled interface can comprise primary andsecondary coils. The at least one implantable device can comprise anenclosure with an extension extending from the enclosure, wherein theprimary coil can be positioned in the enclosure and the secondary coilcan be positioned in the extension. The extension can comprise at leastone of a lead or an antenna. The primary and second coils can compriseplanar coils. The planar coils can comprise matching planar coils. Theprimary and secondary coils can comprise co-planar coils. The at leastone implantable device can comprise an enclosure, wherein the enclosurecan comprise a convex and/or concave port proximate a co-planar coil.The AC coupled interface further can comprise a ferrite core. The ACcoupling interface can comprise a capacitive coupling interface. The atleast one implantable device can comprise an implantable enclosure andan extension, wherein the AC coupling interface comprises a first platein the enclosure and a second plate in the extension.

In some embodiments, the at least one implantable device is configuredto electrically stimulate tissue. The electrical stimulation can becontrollable by configuring parameters wherein the configurableparameters are selected from the group consisting of: amplitude;frequency; pulse width; polarity; pulse shape; and combinations thereof.The electrical stimulation parameters can be configured to have thefollowing parameters: frequency in the range between 1 Hz and 50 kHz;pulse width in the range between 1 microsecond and 50 milliseconds;amplitude in the range of 0.1 and 20 mA. The electrical stimulationparameters can be configured to have the following parameters: frequencyin the range between 40 and 150 Hz; pulse width in the range between 100and 500 microseconds; amplitude in the range of 0.2 and 10 mA. Theelectrical stimulation parameters can be configured to have thefollowing parameters: frequency in the range between 2 and 20 kHz; pulsewidth in the range between 10 and 500 microseconds; amplitude in therange of 0.1 and 10 mA.

In some embodiments, the at least one implantable device is configuredto mechanically interact with tissue. In some embodiments, the at leastone implantable device is constructed and arranged to achieve aninteraction with tissue selected from the group consisting of: inducingmotion; moving tissue; rotating tissue; squeezing tissue; expandingtissue; repositioning at least a portion of the implantable devicewithin tissue; and combinations thereof. The at least one implantabledevice can be constructed and arranged to provide motion selected fromthe group consisting of: vibrations; impulses; linear displacements;angular displacement; and combinations thereof. The at least oneimplantable device can be constructed and arranged to provide motion atone or more frequencies between 1 Hz and 50 KHz. The at least oneimplantable device can be constructed and arranged to provide motionwith adjustable duty cycles. The at least one implantable device cancause the mechanical interaction by application of a force selected fromthe group consisting of: electromagnetics force; magnetic force;piezoelectric force; thermal expansion force; and combinations thereof.The at least one implantable device can comprise a lead with a tipportion, and the mechanical interaction with tissue comprises impartingof a force on tissue by the tip portion. The at least one implantabledevice can be further constructed and arranged to electrically stimulatetissue.

In some embodiments, the at least one implantable device comprises aconnection hub. The at least one implantable device further can comprisemultiple leads and a controller, wherein the connection hub isconfigured to operably connect the multiple leads to the controller. Theconnection hub can comprise a first connection hub, wherein the at leastone implantable device further comprises a second connection hubconnected to the first connection hub.

In some embodiments, the at least one implantable device furthercomprises an MRI effect reducing assembly. The MRI effect reducingassembly can comprise a component selected from the group consisting of:heat sink; heat spreader; shielding; high heat conduction element;active shorting element; passive shorting element; reed switch;mechanical switch; switch activated before and/or during MRI use;parallel electrical connections; current diverters; and combinationsthereof.

In some embodiments, the at least one implantable device furthercomprises an anchor element configured to attached at least a portion ofthe at least one implantable device to tissue. The anchor element cancomprise an element selected from the group consisting of: element withtexturized pattern; eyelet; suture hole; suture; barb; clamp; clamp withsuture hole; staple; and combinations thereof. The at least oneimplantable device can comprise a lead, wherein the lead is positionedon the anchor element.

In some embodiments, the at least one implantable device furthercomprises a marker configured to identify the three dimensionalorientation of at least a portion of the at least one implantabledevice. The marker can comprise a radiopaque marker. The at least oneimplantable device can comprise a lead with a tip portion, wherein themarker is positioned on the lead tip portion.

In some embodiments, the at least one implantable device furthercomprises a needle injection assembly configured to slidingly receive atleast a portion of the at least one implantable device and position theat least a portion in tissue.

In some embodiments, the at least one external system comprises a singlediscrete component.

In some embodiments, the at least one external system comprises multiplediscrete components such as multiple external devices or patches. Insome embodiments, the at least one external system comprises a firstdiscrete component, a second discrete component and a tether configuredto transfer power and/or communication between the first discretecomponent and the second discrete component. In some embodiments, the atleast one external system comprises a first discrete component, a seconddiscrete component and a wireless link configured to transfer powerand/or communication between the first discrete component and the seconddiscrete component. The at least one external system can be configuredto transfer data between the multiple discrete components.

In some embodiments, the at least one external device comprises atransmission antenna configured to be positioned proximate the patient'sskin. The at least one implantable device can comprise an implantableantenna, wherein the transmission antenna is configured to be positionedproximate the patient's skin at a location proximate the implantableantenna.

In some embodiments, the at least one external system comprises acommunication protocol for interfacing with a component selected fromthe group consisting of: computer; smart phone; handheld device;Internet; LAN; and combinations thereof. The communication protocol canbe configured to transfer data at a rate up to and exceeding 20 Mbps.The communication protocol can be configured to transfer data at a ratein the range of 0.1 and 50 Mbps.

In some embodiments, the at least one external device comprises at leastone antenna. The at least one antenna can be constructed and arranged tobe removably attached to the patient's skin. The at least one antennacan comprise an attachment element selected from the group consistingof: adhesive; belt; band; strap; and combinations thereof. The at leastone external system can comprise a controller, wherein the at least oneantenna is configured to send and/or receive information to and/or fromthe controller. The at least one antenna can be configured to sendand/or receive the information via a wired connection. The at least oneantenna can be configured to send and/or receive the information via awireless connection. The wireless connection can comprise a connectionselected from the group consisting of: Bluetooth; WiFi; ZigBee; Qualcomm2net; MICS; ISM; WMTS; MedRadio; MNN; MBAN; cellular communications;RFID; and combinations thereof. The at least one antenna can comprise apower supply. The at least one antenna can comprise a flexiblesubstrate. The at least one antenna can comprise a skin-printed antennacomprising epidermal electronics. The at least one antenna can comprisemultiple antennas. The multiple antennas can be configured to transmitpower and/or communication simultaneously. The multiple antennas can beconfigured to relay received commands from one or more controllers toone or more implantable devices or from one or more implantable devicesto one or more controllers while powering one or more implantabledevices. The multiple antennas can be configured to function as part ofa network. The at least one antenna can comprise a tuning element. Thetuning element can be configured to tune performance based on antennaposition, orientation and/or operating environment. The tuning elementcan be configured to automatically tune the performance.

In some embodiments, the at least one external device comprises adisposable portion. The disposable portion can comprise a componentselected from the group consisting of: at least one antenna; multipleantennas; an attachment element; an adhesive attachment element; andcombinations thereof. The at least one external device further cancomprise a reusable portion. The reusable portion can comprise acomponent selected from the group consisting of: power supply;rechargeable battery; controller; electronics; one or more antennas;user interface; and combinations thereof.

In some embodiments, the at least one external device comprises at leastone enclosure. The at least one enclosure can surround at least one of apower supply or a controller. The apparatus can further comprise anantenna tethered to the at least one enclosure. The apparatus canfurther comprise an antenna positioned in the enclosure.

In some embodiments, the at least one external system comprises a userinterface. The user interface can comprise at least one user inputcomponent. The user interface can comprise at least one user outputcomponent. The user interface can comprise a component selected from thegroup consisting of: button; touchscreen display; knob; keyboard;keypad; display; microphone; light; speaker; and combinations thereof.The at least one external device can comprise an attachment assembly,wherein the user interface is positioned on the attachment assembly.

In some embodiments, the at least one external device further comprisesan attachment assembly, at least one antenna, a controller and a powersupply. The attachment assembly can position the antenna proximate thepatient's skin. The attachment assembly can position the controllerrelative to the patient. The at least one antenna can comprise anattachment element configured to attach the antenna on the patient'sskin at a location remote from the attachment assembly. The at least oneimplantable system can comprise multiple implants, wherein the at leastone antenna can comprise multiple antennas each comprising an attachmentelement and each configured to be positioned on the patient's skin atlocations proximate different of the multiple implants. The attachmentassembly can position the power supply relative to the patient. Theattachment assembly can comprise an attachment element selected from thegroup consisting of: belt; band; strap; article of clothing; adhesive;and combinations thereof. The power supply can comprise multiple powersupplies positioned on different locations of the attachment assembly.

In some embodiments, the wireless transcutaneous transmissions comprisetransmissions selected from the group consisting of: powertransmissions; data transmissions; transmissions of synchronizationmarkers; transmission of a training sequence; and combinations thereof.

In some embodiments, the overall system further comprises at least onesensor configured to provide a signal. The apparatus can be configuredto provide apparatus diagnostic information based on the sensor signal.The implantable device can comprise the at least one sensor. The overallsystem can be configured to provide patient physiologic informationbased on the sensor signal.

In some embodiments, the overall system further comprises a trialinginterface configured to operate the at least one implantable deviceduring implantation of the at least one implantable system. The trialinginterface can be configured to enable the patient to provide feedbackabout sensation of paresthesia, its location and/or comfort level. Thetrialing interface can be configured to provide information related tomultiple stimulation parameters and/or multiple electrodeconfigurations. The trialing interface can be configured to provideinformation related to the acceptability of one or more stimulationparameters and/or placement of the at least one implantable system. Theat least one implantable device can comprise at least one electrode,wherein the trialing interface can be configured to provide informationrelated to placement of the at least one electrode. The trialinginterface can comprise a docking element configured to operativelyengage the at least one implantable device. The at least one implantabledevice can comprise a lead, wherein the docking element can beconfigured to operatively engage the lead. The docking element can beconfigured to at least partially surround a portion of the at least oneimplantable device. The docking element can be configured to wirelesslycouple to the at least one implantable device. The docking element cancomprise radio-absorptive and/or radio-reflective materials. The dockingelement can comprise a connector configured to electrically connect tothe at least one implantable device. The trialing interface can comprisea search algorithm configured to provide information related to theacceptability of one or more stimulation parameters and/or placement ofthe at least one implantable device. At least a portion of the at leastone implantable device can be re-positionable, wherein the trialinginterface can be configured to provide re-positioning information. Theat least one implantable device can comprise a lead comprising one ormore electrodes, wherein the trialing interface can be configured tomate with the lead and directly drive the electrodes. The at least oneimplantable device can comprise an antenna interface, wherein thetrialing interface can provide an RF signal to the antenna interface.The external device can provide an RF signal with a similar carrierfrequency to the RF signal of the trialing interface.

In some embodiments, the overall system further comprises a testingassembly comprising a power supply and an RF interface, wherein the RFinterface is configured to mimic an antenna of the at least one externaldevice. The testing assembly can be configured to provide a signal tothe at least one implantable device.

In some embodiments, the at least one implantable device is implantablein (e.g. within, on and/or proximate)one or more of the following sites:the tibial nerve (and/or sensory fibers that lead to the tibial nerve);the occipital nerve; the sphenopalatine ganglion; the sacral and/orpudendal nerve; target sites in the brain, such as the thalamus; thevagus nerve; baroreceptors in a blood vessel wall, such as in thecarotid artery; along, in, or proximal to the spinal cord; one or moremuscles; the medial nerve; the hypoglossal nerve and/or one or moremuscles of the tongue; cardiac tissue; the anal sphincter; peripheralnerves of the spinal cord, including locations around the back; thedorsal root ganglion; and motor nerves and/or muscles.

In some embodiments, the overall system is configured to stimulate oneor more of: tibial nerve (and/or sensory fibers that lead to the tibialnerve); the occipital nerve; the sphenopalatine ganglion; the sacraland/or pudendal nerve; target sites in the brain, such as the thalamus;the vagus nerve; baroreceptors in a blood vessel wall; the spinal cord;one or more muscles; the medial nerve; the hypoglossal nerve and/or oneor more muscles of the tongue; cardiac tissue; the anal sphincter;peripheral nerves of the spinal cord; the dorsal root ganglion; andmotor nerves and/or muscles.

In some embodiments, the overall system is configured to stimulate totreat one or more of: migraine; cluster headaches; urge incontinence;tremor; obsessive compulsive disorder; depression; epilepsy;inflammation; tinnitus; high blood pressure; pain; muscle pain; carpaltunnel syndrome; obstructive sleep apnea; cardiac arrhythmia or othercardiac disease or disorder that could benefit from pacing ordefibrillation; dystonia; interstitial cystitis; gastroparesis; obesity;fecal incontinence; bowel disorders; chronic pain; compromised mobility;spinal cord stimulation (SCS) for heart failure.

In some embodiments, an implantable device may comprise a sealed (e.g.,hermetically sealed) enclosure and one or more of the implantabledevices may form a network with external components, forming awirelessly communicating system that may allow accommodation ofdifferent patients and therapies and ensure reliability, precisetherapy, and enable many treatment options.

In some embodiments, provided are electrode configurations for tissueinterfaces and patterns of electric field coverage, and leadconstructions including standard leads, paddles, bifurcated leads, andconnectorized interfaces. Spinal cord stimulation (SCS) treatments oftenrequire multiple leads, and interfacing the systems and devicesdescribed herein with standard approaches can greatly simplify theiruse. SCS and peripheral nerve stimulation can both take advantage ofmulti-channel stimulation among multiple leads, making this capabilityimportant for the systems and devices described herein. Additionalconfigurability in both electrodes and leads can support new treatmentoptions and refinements.

In some embodiments, provided are implantable antennas constructed inenclosures with orthogonal orientations and tethering options forconnections. Sealed devices can ensure longevity of the implant,minimize the need for explantation, and increase safety. Configurationswith multiple antennas, particularly in orthogonal orientations, canincrease reliability and make the overall system more user-friendly.

In some embodiments, provided are power management systems with anonboard controller and pulse generator on the implant capable ofproducing custom waveforms. Energy storage can allow for anintelligently designed system that decouples power transfer fromstimulation waveforms or sensor operation. Custom waveforms can allowfor adaptive and emerging therapies.

In some embodiments, provided are implantable devices with anattached/connected lead and delivery assemblies that include one or moreof: functional elements, such as electronics or antennas; connectorizedinterchangeable interfaces; sensing elements or other accessories; or,custom, modified delivery needles. Interchangeable operation with avariety of standard interfaces or leads can increase the versatility ofthe overall system. Functional elements distributed along leads canincrease functionality or address specific use cases while operatingwith the same implantable system. The modified delivery system can allowfor simple, minimally-invasive delivery that is very similar to thestandard of care.

In some embodiments, the delivered or implantable device includeselements with controllable stiffness or designed stiffness that supportsthe implantation location. Controllable stiffness and rigidity can guideand anchor the implant to precise locations. Using a sheath or separatestructural component can aid the implantation procedure and be removedafter the desired location is reached.

In some embodiments, provided are four or more stimulation channels thatcan be configured with an AC-coupled interface in the device or in thestructural connection. Multi-channel stimulation can be enabled by theintelligence of the overall system, and can complicate charge balance.AC-coupling can be a fail-safe charge balance mechanism, andincorporating it in structural elements can minimize physical size.

In some embodiments, the implantable device can provide configurableneuromodulation at low and high frequency with different nerveinterfaces. Paresthesia therapies can operate with lower frequencies,and pain-blocking therapies can operate at high frequencies, and theoverall system can be capable of both. Mechanical nueromodulation andinterfaces can induce therapies without electrical contact to nerves andwith significantly less power.

In some embodiments, the implantable system can incorporate a connectionhub that can connect multiple implantable devices and leads together.Interchangeable components can allow for extendable systems with avariable number of leads and devices working together, which can usefulfor spinal cord stimulation (SCS) because patients often requiremultiple leads.

In some embodiments, an implantable device comprises one or more of: MRIcompatibility elements, tissue anchors, markers for detectingorientation, and/or sliding delivery system. Short leads and avoidanceof magnetic materials can minimize risks associated with MRIcompatibility, though additional elements can provide furtherprotection. Tissue anchors can minimize lead migration and motion of theantennas. The ability to detect orientation can assist implantation andcan inform the operation of the external, for example, by adjustingpolarization of the antennas. Versatile delivery systems can allow fornew implantation sites and new treatments, or differently structuredimplants.

In some embodiments, the external device configurations may include: oneor more discrete components/enclosures; one or more antennaconfigurations/attachments outside the body; wired or wirelessconnections with a controller or peripheral devices; antenna arrays;tunable elements on the antenna; disposable and/or reusable portions;and/or, multiple user interface configurations. Configurations withmultiple discrete components (e.g., smaller components) may be morecomfortable to the patient because less bulky components can be moreflexibly placed. Multiple discrete components can form a network andoperate with multiple implantable devices. Different configurations forattaching the antenna can give the overall system flexibility duringusability testing. The external system configuration can includemultiple discrete components that are attached with wires and/or it caninclude elements that communicate without wires, allowing forsignificant flexibility. The ability to communicate peripherally canallow for remote programming from existing devices, such as with aBluetooth connection to a tablet. Antenna arrays can desensitizepositioning requirements and simplify powering of multiple devices. Thetunable elements can allow for increased link performance, improvedefficiency and reliability. Disposable elements may offer advantagesfrom a cost or business perspective, and may simplify certain designelements. User interfaces can be custom designed or implemented throughexisting devices, and can include standard protocols.

In some embodiments, provided is an external device with an attachmentassembly, one or more antennas, a controller, and a power supply. Thegarment or system for attaching can distribute the power supplies and/orantennas in the most comfortable way while maintaining reliableoperation with one or more implants.

In some embodiments, provided may be wireless transcutaneoustransmissions that include power and/or data with optional sensingelements that can collect diagnostic or physiological parameters.Wireless power combined with data can enable the described benefits ofmidfield operation, and incorporating sensors enables closed-loopsystems.

In some embodiments, provided may be a trialing interface for theimplantable device that can include: a wireless or wired connection withthe implant; elements for feedback of electrode positioning; dockinginterface; and/or, information for re-positioning the implant. Atrialing interface can ensure seamless operation of our device in asurgical setting, simplifying use by the doctor. Feedback of electrodepositioning can ensure the electrodes have good contact with tissue andare placed appropriately. A wireless docking port can allow theform-factor system to be tested in a controlled way prior toimplantation, and can allow the therapy coverage to be evaluated.Implant positioning can influence the antenna link performance, andhaving readily available information during implantation can ensure theantenna link functions reliably.

In some embodiments, provided may be a testing assembly comprising an RFtesting interface for the device prior to or after implantation. Thetesting assembly can verify implant functionality immediately precedingimplantation, and can provide other diagnostics on the deviceperformance. This verification can ensure devices are implanted in aneffective (e.g., working) configuration, and can allow for easyverification of implantable devices.

The systems, devices, and methods described herein may be appropriatefor a variety of implantation sites, nerves for stimulation, andtargeted indications. The flexibility of the systems and devicesdescribed herein can allow for a variety of therapies to be providedthroughout the body.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the present disclosure are set forth withparticularity in the appended claims. A better understanding of thefeatures and advantages of the inventions of present disclosure will beobtained by reference to the following detailed description that setsforth illustrative embodiments, in which the principles of the presentdisclosure are utilized, and the accompanying drawings of which:

FIG. 1 shows Screw or Part Grabber devices that have a similar mechanismof action compared to embodiments of tissue attachment method, accordingto many embodiments;

FIG. 2 illustrates the described attachment mechanism operating withtissue;

FIGS. 3A, 3B, and 3C illustrate the described attachment apparatus witha single group of attaching elements and a method of attachment totissue;

FIGS. 4A, 4B, and 4C illustrate the described attachment apparatus withmultiple groups of attaching elements and a method of delivering andattaching said apparatus to target tissue;

FIG. 5 illustrates the structure of a vertebrae and a description of thedifferent parts;

FIG. 6 illustrates the locations of the dorsal root and the dorsal rootganglion with respect to the spinal column;

FIG. 7 illustrates a neuromodulation therapy involving multiplemodulation sites in which some are active and some are not;

FIG. 8 illustrates several attachments to different tissues, nerves, ornerve bundles using the methods described herein;

FIG. 9 illustrates a diagram of the sympathetic nervous system tohighlight which nerves can be targeted for different therapies ordiagnostics;

FIG. 10 illustrates the basic structure of a neuron with labeled parts;

FIG. 11 illustrates the classifications of different types of pain;

FIG. 12 illustrates ramus communicans depicted as a schematic;

FIG. 13 illustrates additional depictions of spinal nerves andstructures;

FIG. 14 illustrates a variation of flexible tissue interfaces thatconnect devices and tissues;

FIG. 15 illustrates an additional variation of flexible tissueinterfaces for sensing or modulation of tissue;

FIG. 16 illustrates different pin configurations for securing the tissueinterface in place;

FIG. 17 illustrates a flexible substrate using pins or screws formultiple tissue connections;

FIG. 18 illustrates a flexible structure that can wrap around targettissues to attach to them;

FIG. 19 illustrates a variation of the flexible structure that wrapsaround targeted tissues using pins or screws.

FIG. 20 shows a schematic illustrating the envisioned application ofembodiments of the external system operating with one or moreimplantable devices.

FIG. 21 shows a schematic of a basic block diagram of an implantabledevice with power harvesting and management, two-way communications, adigital controller, a pulse generator, and an interface for one or moresensors and electrodes.

FIG. 22 shows a schematic of a basic block diagram of the externalsystem with the ability to transfer power and communicate with thedevice or other hardware as well as sensor or electrode interfaces.

FIGS. 23a, 23b, 23c, and 23d show schematics illustrating userinterfaces networked with one or more external devices.

FIG. 24 shows a schematic illustrating a method for wirelesslyrecharging the external device(s).

FIG. 25 shows an exemplary external device with a removable rechargeablebattery.

FIG. 26 shows an exemplary external device implemented as a flexiblepatch.

FIG. 27 shows a schematic of a setup for networking a reader withmultiple devices.

FIG. 28 shows a schematic of a configurable receiver that can interfacewith sensors, transducers or other devices.

FIG. 29 shows waveforms illustrating the ASK-PW modulation method fordata transmission.

FIG. 30 shows waveforms illustrating an ASK method using multi-levelencoding.

FIG. 31 shows circuit diagrams for modulation methods and circuits forhigh frequency ASK modulation with adjustable depth.

FIG. 32 shows a circuit diagram of a direct conversion receiver fordetecting reflected energy.

FIG. 33 shows circuit diagrams of an analog sensor or body conductioninterface.

FIG. 34 shows schematics of a method for assigning a unique ID todevices.

FIG. 35 shows a schematic of a timing diagram for a TDMA protocol withmultiple external and/or implantable devices.

FIG. 36 illustrates an embodiment of an overall system including aneedle-injected implantable system to be used with an external system;consistent with the present inventive concepts.

FIG. 37 illustrates a basic system diagram of an implantable system withpower harvesting and management, two-way communications, a digitalcontroller, a pulse generator, and an interface for one or more sensorsand electrodes; consistent with the present inventive concepts.

FIG. 38 illustrates a basic block diagram of an implantable system withthe ability to receive power and communicate with the external system orother hardware; consistent with the present inventive concepts.

FIG. 39 illustrates an external device with a power source, controller,and tethered antennas; consistent with the present inventive concepts.

FIG. 40 illustrates an external device with a power source, controller,and one or more tethered antennas; consistent with the present inventiveconcepts.

FIG. 41 illustrates an external device with a power source, controller,and antenna integrated in a single enclosure; consistent with thepresent inventive concepts.

FIG. 42 illustrates an external device with a power source, acontroller, and one or more untethered antennas with each antennaattached to a power source and a communications relay; consistent withthe present inventive concepts.

FIGS. 43a, 43b, 43c, and 43d illustrate multiple external devicesoperating in a network with a handheld controller; consistent with thepresent inventive concepts.

FIG. 44 illustrates an external device with a power source, controller,and one or more antennas integrated into an attachment assembly;consistent with the present inventive concepts.

FIG. 45 illustrates an external device with a power source andcontroller integrated into an attachment assembly with and one or moretethered antennas; consistent with the present inventive concepts.

FIG. 46 illustrates an external device integrated into an attachmentassembly with one or more distributed antennas and/or distributed powersources; consistent with the present inventive concepts.

FIG. 47 illustrates an external device with a power source, controller,and antenna next to an implantable device.

FIG. 48 illustrates an implantable device with an encapsulated housing,a tethered antenna, and a lead; consistent with the present inventiveconcepts.

FIG. 49 illustrates an implantable device with an encapsulated housingand a lead; consistent with the present inventive concepts.

FIG. 50 illustrates an implantable device with an encapsulated housing,orthogonal antennas, and a lead; consistent with the present inventiveconcepts.

FIG. 51 illustrates an implantable device integrated into a lead withantennas and electrodes; consistent with the present inventive concepts;

FIG. 52 illustrates an implantable device with a cylindricalencapsulated housing, a lead, electrodes, electronics, and an antenna;consistent with the present inventive concepts.

FIG. 53 illustrates an implantable device with a rectangularencapsulated housing, a lead, and electrodes; consistent with thepresent inventive concepts.

FIG. 54 illustrates an implantable device with an encapsulated housingand feedthroughs for the electrodes with no lead; consistent with thepresent inventive concepts.

FIG. 55 illustrates example waveforms for mechanical motion that canmodulate tissue; consistent with the present inventive concepts.

FIG. 56 illustrates a device housing with bifurcated or multiple leads;consistent with the present inventive concepts.

FIG. 57 illustrates a housing with multiple connection interfaces aswell as a connection hub; consistent with the present inventiveconcepts.

FIG. 58 illustrates a wireless AC-coupled interface implemented usinginductive coupling; consistent with the present inventive concepts.

FIG. 59 illustrates a wireless AC-coupled interface implemented usingcapacitive coupling; consistent with the present inventive concepts.

FIG. 60 illustrates various implantable device embodiments with styletsand lumens for stylets and other tools; consistent with the presentinventive concepts.

FIG. 61 illustrates cross-sectional view of several embodiments of alead, showing conductors of an interconnect, lumen for a stylet, andsheath around a lead; consistent with the present inventive concepts.

FIG. 62 illustrates a lead implantation sheath with a guide wire, or alumen inserted in it; consistent with the present inventive concepts.

FIG. 63 illustrates several embodiments of a clamp or anchor; consistentwith the present inventive concepts.

FIG. 64 illustrates several embodiments of extension devices which canconnect to the connector interface on an implantable device, includingone or more antennas, trialing interface, energy storage, and interposerconnector; consistent with the present inventive concepts.

FIG. 65 illustrates an implantable device with distributed antennas anda trialing interface; consistent with the present inventive concepts.

FIG. 66 illustrates an implantable device with electrodes in epiduralspace, a wireless trialing interface for intraoperative trialing, and anexternal device for postoperative operation or wireless trailing;consistent with the present inventive concepts.

FIG. 67 illustrates connectorized interface of the implantable device,including implant package, lead, and antenna; consistent with thepresent inventive concepts.

FIG. 68 illustrates adapters, interposers, and connection hubs;consistent with the present inventive concepts.

FIG. 69 illustrates connectorized implantable device with active leadsconnected in series, forming a diamond pattern; consistent with thepresent inventive concepts.

FIG. 70 illustrates an example of a radio-opaque marker in differentangles and orientation; consistent with the present inventive concepts.

FIG. 71 illustrates a two-piece needle introducer with hinges forminimally invasive implantation of an implantable device; consistentwith the present inventive concepts.

FIG. 72 illustrates a two-piece needle introducer held together with asheath for implantation of an implantable device; consistent with thepresent inventive concepts.

FIG. 73 illustrates a simple circuit model for a typical electrode.

FIG. 74 illustrates a chart of output current versus output bias voltagefor a stimulator, according to many embodiments.

FIGS. 75a and 75b show current paths for a single-channel stimulator,according to many embodiments.

FIGS. 76a and 76b show current paths for a single-channel stimulatorusing a hybrid approach for stimulation and recovery, according to manyembodiments.

FIG. 77 shows a circuit diagram of a single-channel stimulator using agrounding load during recovery, according to many embodiments.

FIG. 78 shows a circuit diagram of an electrode pad leakage monitoringscheme, according to many embodiments.

FIG. 79 shows a circuit diagram of a scheme to mitigate single-pointon-chip failures, according to many embodiments.

FIG. 80 shows a circuit diagram of scheme to achieve charge-balancedstimulation and protect tissue against DC current, according to manyembodiments.

FIG. 81 shows a circuit diagram of an H-bridge stimulator architecture,according to many embodiments.

FIG. 82 show a circuit diagram of a scheme using regulated electrodebias-voltage for safe neural stimulation, according to many embodiments.

FIG. 83 shows a circuit diagram of a scheme of a current-sink H-bridgeapproach, according to many embodiments.

DETAILED DESCRIPTION

The present disclosure relate to neuromodulation methods, systems, andapparatus for the treatment of pain management as well as otherconditions or disorders. In particular, many embodiments provide forprecise, controlled modulation of specific nerves or tissues to inducephysiological effects. Additionally, embodiments that incorporateinformation for diagnostics or improved therapeutic efficacy aredescribed. Also, apparatus and devices are described that improve thetherapies or the diagnostics.

There are different types of pain which are classified into two majorcategories: nociceptive and non-nociceptive pain, as can be seen in painclassification 1100 shown in FIG. 11. Nociceptive pain can arise fromthe stimulation of specific pain receptors. These receptors can respondto heat, cold, vibration, stretch, and chemical stimuli released fromdamaged cells. Non-nociceptive pain can arise from within the peripheraland/or central nervous system. Specific receptors do not exist here,with pain being generated by nerve cell dysfunction. Nociceptive paincan be further categorized into somatic and visceral pain.Non-nociceptive pain can be further categorized into neuropathic andsympathetic pain. Based on these classifications and on the actualorigins of pain, various treatments may be more effective than others.

Somatic pain typically originates in tissue such as skin, muscle,joints, bones, and ligaments and is commonly referred to asmusculo-skeletal pain. In this pain process, specific receptors, knownas nociceptors, may be activated for heat, cold, vibration, stretch(muscles), inflammations (such as cuts and sprains which cause tissuedisruption), and oxygen starvation (ischaemic muscle cramps), causingthe sensation of pain. The characteristics of pain may be that it isoften sharp and well-localized, and can often be reproduced by touchingor moving the area or tissue involved. While there are some known usefulmedications to treat somatic pain, such as combinations of paracetomol,weak or strong opioids, and NSAIDs, it may be more preferable to treatthis pain via neuromodulation. This way of treatment may especially beuseful in cases of patients who have side effects to medication,medically refractive pain cases, chronic pain, and other cases wheremedication is not effective or not preferred.

Visceral pain typically originates from internal organs of the main bodycavities. There are three main cavities—thorax (heart and lungs),abdomen (liver, kidneys, spleen and bowels), and pelvis (bladder, womb,and ovaries). The receptors activated in this type of pain may bespecific receptors (nociceptors) for stretch, inflammation, and oxygenstarvation (ischemia). The characteristics of this pain may include painthat is often poorly localized, and may feel like a vague deep ache,sometimes being cramping or colicky in nature. It can frequently producereferred pain to the back, with pelvic pain referring pain to the lowerback, abdominal pain referring pain to the mid-back, and thoracic painreferring pain to the upper back. Some useful medications to whichvisceral pain responds are weak and strong opioids.

Nerve pain, which falls under non-nociceptive pain category, canoriginate from within the nervous system itself—also known as pinchednerve or a trapped nerve. The pain may originate from the peripheralnervous system (the nerves between the tissues and the spinal cord), orfrom the central nervous system (the nerves between the spinal cord andthe brain). The causes may be due to any of the following processes:Nerve Degeneration—multiple sclerosis, stroke, brain hemorrhage, oxygenstarvation; Nerve Pressure—trapped nerve; Nerve Inflammation—torn orslipped disc; Nerve Infection—shingles and other viral infections. Thenervous system itself does not have specific receptors for pain(non-nociceptive). Instead, when a nerve becomes injured by one of theprocesses named above, it becomes electrically unstable, firing offsignals in a completely inappropriate, random, and disordered fashion.Characteristics of this pain after being interpreted by the brain aspain can be associated with signs of nerve malfunction such ashypersensitivity (touch, vibration, hot and cold), tingling, numbness,and weakness. There is often referred pain to an area where that nervewould normally supply e.g. sciatica from a slipped disc irritating theL5 spinal nerve produces pain down the leg to the outside shin and bigtoe i.e. the normal territory in the leg supplied by the L5 spinalnerve. Spinal nerve root pain can also often be associated with intenseitching in the distribution of a particular dermatome. People oftendescribe nerve pain as lancinating, shooting, burning, andhypersensitive. This pain can only be partially sensitive toparacetamol, NSAIDs, opioids. It can be more sensitive toanti-depressants, anti-convulsants, anti-arrhythmics, and NMDAantagonists. Topical capsaicin may also be helpful.

Another type of pain which falls under non-nociceptive pain category issympathetic pain. The reason and source of this pain may be due topossible over-activity in sympathetic nervous system, andcentral/peripheral nervous system mechanisms. The sympathetic nervoussystem controls blood flow to tissues such as skin and muscle, sweatingby the skin, and the speed and responsiveness of the peripheral nervoussystem. This type of pain occurs more commonly after fractures and softtissue injuries of the arms and legs, and these injuries may lead toComplex Regional Pain Syndrome (CRPS). CRPS was previously known asReflex Sympathetic Dystrophy (RSD). Like nerve pain there are nospecific pain receptors (non-nociceptive). The same processes asmentioned above in nerve pain may operate in CRPS. Sympathetic painpresents as extreme hypersensitivity in the skin around the injury andalso peripherally in the limb (allodynia), and is associated withabnormalities of sweating and temperature control in the area. The limbis usually so painful, that the sufferer refuses to use it, causingsecondary problems after a period of time with muscle wasting, jointcontractures, and osteoporosis of the bones. It is possible that thesyndrome is initiated by trauma to small peripheral nerves close to theinjury. Many of the features of sympathetic pain are similar to those ofnerve pain, and therefore nerve pain medications may be useful(anti-depressants, anti-convulsants, and anti-arrhythmics). Drugs whichlower blood pressure by causing vasodilatation (nifedipine) may also beuseful when used in combination. Treatment should include appropriatemulti-modal medications, sympathetic nerve blocks, and intensiverehabilitation combining occupational and physiotherapy. Neuromodulationof these nerves offers an attractive alternative by mitigating orblocking the pain without the side effects of medication.

It can be important to target the right nerves when treating specificpain. For instance, inside a body, somatic pain information istransferred from the origin of pain at nociceptors to the brain viasomatic afferent nerves and nerve structures. Therefore, it can beimportant to target somatic afferent nerves. Posterior nerve rootcontains nerves and nerve bundles that have somatic and sympatheticafferent nerves physically separated from other types of nerves.Targeted nerve modulation of this posterior nerve root can treat painonly without affecting efferent nerves. Therefore, dorsal root, dorsalroot ganglion, pre- or post-ganglionic neural tissue can be modulated tosuppress pain propagation or mask pain. An example is spinal ganglion1210 on the posterior nerve root 1212 as shown in FIG. 12 and otherperspective views including spinal structure 1300 shown in FIG. 13. Itis also possible to modulate spinal nerve, gray and/or white ramuscommunicans to treat pain. However, this modulation may requiremodification in treatment parameters to achieve the same therapeuticeffect without affecting efferent nerves because afferent nerves areonly slightly physically separated from efferent nerves in these otheranatomical structures. In order to target only sympathetic afferentnerves and not somatic afferent nerves, it is possible to target grayand white rami communicantes, which do not contain somatic afferentnerves.

FIG. 12 shows ramus communications as a schematic. The general somaticafferent somatic sensory fibers 1202 may arise from cells in the spinalganglia and may be found in all the spinal nerves, except occasionallythe first cervical, and may conduct impulses of pain, touch,temperature, etc. from the surface of the body through the posteriorroots to the spinal cord and impulses of muscle sense, tendon sense, andjoint sense from the deeper structure. The spinal nerve 1200 may furtherinclude somatic efferent nerves 1201, sympathetic efferent nerves 1203,sympathetic afferent nerves 1206, the cell of dogiel 1214, thesympathetic ganglion 1216, the sympathetic cord 1218, the anterior nerveroot 1220, and the sympathetic ganglion 1222.

FIG. 13 shows other another schematic and a perspective view of thespinal nerve and adjacent anatomical structures 1300. The spinal nerveand the adjacent anatomical structures may comprise grey matter 1305,white matter 1310, the dorsal root 1315, the ventral root 1320, thespinal nerve 1325, the dorsal ramus 1330, the ventral ramus 1335, thewhite ramus 1340, and the gray ramus 1345. The spinal nerve and theadjacent anatomical structures may further comprise the spinal ganglion1350, the anterior root 1355, the posterior root 1360, the posteriordivision 1365, the anterior column 1385 of the vertebrae, the posteriorcolumn 1370 of the vertebrae, the lateral column 1375 of the vertebrae,and the anterior medial fissure 1380.

Particular organs can be targeted via neuromodulation of sympatheticnervous system (SNS). Electrodes or interfaces can be placed at theorigin of SNS, next to thoracolumbar region of the spinal cord (levelsT1-L2), where the shorter preganglionic neurons originate. In additionor instead, electrodes or interfaces can be placed downstream from thepreganglionic neurons, such as at a ganglion, such as one or more of theparavertebral ganglia, where preganglionic neurons synapse with apostganglionic neuron. The electrode positioning can also be done, inaddition to or instead of previously mentioned locations, along the longpostganglionic neurons which extend across most of the body as can beseen in schematic 900 of FIG. 9. The schematic 900 shows the variousregions of the spinal cord and how they affect various target organs.The general illustration of a neuron 1000 is shown in FIG. 10. Theattachment of electrodes to the above-described regions and locations ofthe sympathetic nervous system can be accomplished using methodsdescribed herein. The attachment can be done to ganglia, axons, or otherparts of neurons as seen in FIG. 10. As shown in FIG. 10, the axon 100may comprise a plurality of Schwann cells 1010 covered by myelin sheaths1020. The axon 100 may further comprise nodes of Ranvier 1030. As shownin FIG. 10, the nerve cell 1045 may comprise a nucleus 1050, a soma1055, dendrites 1060, and axon terminals 1065.

Chronic back pain has several existing neuromodulation therapies thattarget nerves in the back and in the spine. Some methods are placed inthe vicinity of these nerves, and some are placed inside specificnerves. There are at least several elements that can dramaticallyimprove the efficacy and safety of these therapies. Precisely locatingthe neuromodulation sites can ensure that only the nerves inducing painor carrying pain signals are targeted and minimize unnecessary andunwanted neuromodulation of surrounding tissues. This precise locationcan potentially reduce the power requirements of the neuromodulationsystem, and can improve efficacy by focusing the energy at the desiredsite, and improves patient comfort by minimizing extraneousneuromodulation, which could affect motor function or induce othersensations. Additionally, the ability to selectively configure theneuromodulation at multiple targeted sites can give flexibility that cangreatly enhance the therapy. Each patient is different and it can bedifficult or impossible to identify the exact type of neuromodulationahead of time, so this flexibility is often crucial. One of the moreeffective sites for treating chronic back pain may be in or around thevicinity of the dorsal root and the dorsal root ganglia. Placing theneuromodulator proximal or distal to either the dorsal root or thedorsal root ganglia as previously described can induce similar therapyto modulating these nerves specifically, and may even be advantageous incertain cases. Additionally, locations on the nerve upstream ordownstream (in relation to the spinal cord) of either the dorsal rootganglia or dorsal root can achieve similar or better efficacy. It can bedifficult to know exactly which dorsal root or dorsal root gangliashould be targeted ahead of time, and in some cases multiple sites canbe targeted for effective treatment. Therefore, methods with controlledmodulation of multiple sites either simultaneously or sequentially canbe important for more effective treatments. Combining any and all ofthese techniques can result in improvement, and the preferred method canmake use of multiple elements with innovative new devices. Methods forattaching, modulating, sensing, and adapting the therapy delivered tothese sites are described in the following sections, as well asapparatus and devices that improve on existing technology.

Chronic pain can also surface in a number of other locations in the bodyfor a variety of reasons. Some cases may be neuropathic in nature, andcan be caused by damage or disease to parts of the somatosensory system.Neuropathic pain can include phantom pain, which is an experience ofpain felt from a part of the body that has been lost or is no longerconnected to the brain through the nervous system. Alternatively, thesecases can be from nociceptive pain, which is caused by stimulation ofnociceptors, which only respond to stimuli of excessive intensity.Another form of chronic pain is psychogenic, which results from certaintypes of mental, emotional, or behavioral factors. Psychogenic pain canbe just as debilitating as pain from other sources. For all these typesof pain, active research is showing promise for neuromodulationtherapies. The higher the precision of the location and profile of theneuromodulation, the higher the efficacy and lower the risk of thetreatment can be. For pain experienced in a specific location,neuromodulation sites could target the specific location of the nerve,as well as in close proximity, including both upstream and downstreamlocations (closer or farther to the spinal cord and brain).Additionally, neuromodulation treatments can target tissues other thannerves, and induce activity that accelerates healing and minimizesdiscomfort. Multiple sites can be targeted either sequentially orsimultaneously with configurable neuromodulation treatments that arebased on physiological responses or other information. This could beespecially useful when the healing occurs in multiple phases, anddifferent tissues are responsible for different aspects of the healingprocess. Combining any and all of these techniques results inimprovement, and the preferred method would make use of multipleelements with innovative new devices. Methods for attaching, modulating,sensing, and adapting the therapy delivered to these sites are describedin the following sections, as well as apparatus and devices that improveon existing technology.

Similarly to chronic pain, many types of acute pain can be treated withneuromodulation methods as well. As an example, research has shownevidence that migraines can be mitigated or eliminated throughmodulation of nerves in the nasal passage, which is likely because oftheir direct connections to the brain. Sphenopalatine ganglion orsphenopalatine nerves are examples of specific nerve structures that canbe stimulated to stop migraines and other headaches. In cases of acutepain, giving the patient or doctor real-time control of theneuromodulation parameters is essential, and having the ability totarget multiple sites can be essential in an effective treatment. Usingany number of methods of modulating nerves, the precise location andcontrol of the parameters can greatly enhance the therapeutic outcome. Afeedback system can incorporate information from the patient in responseto changes in the pain or from directly sensing signals from the tissuesor nerves. The location of the stimulation sites can be at the site ofthe pain or downstream or upstream from it in the nervous system, as inthe example of the treatment for migraines. Methods for attaching,modulating, sensing, and adapting the therapy delivered to these sitesare described in the following sections, as well as apparatus anddevices that improve on existing technology.

In particular methods, the modulation system interface may compriseseveral semi-rigid wires or structures which can extend out of a lumen,which can be flexible, rigid, or semi-rigid. The modulation systeminterface can be placed inside of a delivery system, which may be aneedle, a cannula, introducer, or other system. The curved ends of wirescan allow them to grab around and onto a nerve, ganglion, bundle, orother tissue or anatomical structure, such as around a dorsal rootganglion, dorsal root, muscle, or bone. When the wires are retracted,they may compress together. This mechanism of action can allows theinterface to attach to tissue without needing an explicit anchoringmechanism. The mechanism of action and design is substantially similarto the Screw or Part Grabber devices 100 a and 100 b (also referred toas screw-grabber) that are shown in FIG. 1.

As shown in FIG. 1, the screw-grabber 100 a may be rigid and thescrew-grabber 100 b may be flexible and bendable. Electrodes may beconfigured with similar mechanisms of action to the screw-grabbers 100 aand 100 b and have adapted and modified functionality of grabbing ontonerve ganglia, nerve bundles, nerve tissues, or other tissues. The wireswhich extend out of leads may be isolated at least partially to preventshorting. The tips of the wires can be non-insulated to enable energydelivery to tissue. Alternatively, the wires may simply function as ananchor and/or inactive electrode (ground or reference electrode). Theactive electrode could be placed within nerve tissue and can be in theform of a needle which can penetrate through neural tissue, therebyenabling current flow from the inside of the neural tissue to thereference electrodes which are positioned on the outside of the neuraltissue.

For neuromodulation, the attaching structures can comprise wires thatare conductive and can be electrically connected to the same contact orconnected to separate contacts on the neuromodulator system. Somepossible connection mechanisms and method examples are shown in FIGS. 2,3A, 3B, 3C, 4A, 4B, and 4C. If connected to different contacts, eachwire can have a potential to be individually controlled and thus canenable current steering which can be beneficially used to target energydelivery to particular nerves and avoid delivery to unintended nervesand tissue. If electrically connected together, all the wires do nothave to be isolated and can act as a single (distributed) electrode.This connection configuration would increase the surface area of theelectrode and lower tissue/electrode impedance. This option, however,may require another electrode (e.g. a return electrode) to complete theelectrical circuit. Such a circuit-completing electrode can be placed ona side of the neuromodulator (e.g. on the housing of the neuromodulator)away from attached electrodes, can be selected as one of the attachedelectrodes, can be positioned in the center of the attached electrodes,or can be a separate attached electrode using any attachment method. Themethod similar to a Screw or Part Grabber can also feature one or moreinternal needle-like (or bayonet-like) extensions in the middle of thewires, for example similar in structure to a BNC connector. This centralextension can penetrate through tissue when attaching the electrode tothe desired tissue, and eventually reside inside of the tissue. Theextension protruding into the tissue could be programmed to sourceand/or sink current, while external anchoring (grabbing) wires or aseparately attached system would have the opposite polarity to thecentral extensions. In other implementations, multiple center wires orneedle-like extensions could be included and could act as separateelectrodes. Some of the potential advantages of a tissue grabbing systemare that these elements provide a way to anchor the modulation interfacewithout a complex procedure. Also, the electrodes of the presentinvention can be in a compact form which is well-suited for deliverythrough a lumen, such as a lumen of a cannula, catheter, needle, orintroducer. A simple mechanism, such as a mechanism enabling pressing ofa button, can open up the wires or electrodes in proportion to level ofactivation of the mechanism (such as the amount of depression of thebutton). Upon release of the mechanism, the electrodes transition totheir original state of compression. When advanced close to a nerve,nerve bundle, or other tissue and upon release of the mechanism, theelectrodes or wires wrap around the tissue and secure them in place.Additionally, when the needle-like center electrode is not used, orotherwise when the tissue is not penetrated, undesirable side-effectscan be reduced and/or the healing process can be accelerated. Also, thismethod can provide a self-adjustable way to anchor the modulationinterface to varying size tissue or nerves without having to customizethese electrodes for a particular patient. Multiple attached modulatorsystem configurations utilizing a variety of screw-grabber anchoringmechanisms are illustrated in FIG. 8.

Referring back to FIG. 2, screw-grabber connectors or electrodes(anchoring mechanisms) can be used to attach to any tissue, such as anerve and nerve ganglion 200. In a step 201, the electrode may beadvanced so that its tip is in proximity to a nerve. In a step 202, theconnecting elements may be opened by engaging a remote activator such asa button. In a step 203, the connecting elements may be openedsufficiently wide to be able to grab onto the desired tissue (nerveganglion in this case). In a step 204, the connecting elements may startclosing by disengaging the remote activator (releasing the button). In astep 205, the remote activator may be completely disengaged to anchorthe electrodes in place, completing the procedure. The screw-grabberconnectors or electrodes may be removed by inversing these steps.Specifically, to remove these interfaces, one would first start engagingthe remote activator until connecting elements are sufficiently open tobe able to remove them from the target tissue. Then, the connectingelements may be removed from the target tissue. Once connecting elementsare no longer overlapping with the target tissue, the removal activatorcan be fully or partially disengaged to close the connecting elements,reverting it back to the step 201. The screw-grabber connectors orelectrodes can then be completely removed from the body.

FIGS. 3A-3C show an apparatus and method of securing an implant body 300to target tissue 340. The implant body 300 may be positioned within asliding tube 310. The implant body 300 may comprise feed-throughs 320for connecting elements 330 for grabbing on to target tissue 340, suchas nerve ganglion. As shown in FIGS. 3B and 3C, the sliding tube 310 canbe advanced in the direction of arrow 335 to secure the connectingelements 330 to the target tissue 340. FIG. 3B shows the sliding tube310 slightly advanced to push the connecting elements 330 to the targettissue. FIG. 3C shows the sliding tube 310 fully advanced to fully pressthe connecting elements 330 against the target tissue, securing theimplant body 300 against the target tissue 340. The sliding tube 310 canbe flexible or rigid.

FIGS. 4A-4C show an apparatus and method of securing an implant body 400with multiple groups of connecting elements 430 to target tissue 440.The apparatus may utilize multiple groups of connecting elements 430which can be compressed or opened by using at least one sliding tube 410per group of connecting elements 430. The connecting elements 430 may becoupled to the implant body 400 through feed-throughs 420. Each tube 410may push connecting elements 430 together similar to the action of ascrew-grabber device to secure each group of connecting elements 430 tothe desired location on the target tissue 440. FIGS. 4A-4C show asequence of attaching the implant body 400 to the target tissue 440. Asshown in FIG. 4A, the implant body 400 may be positioned completelywithin an introducer 450 with all groups of connecting elements 430compressed. As shown in FIG. 4B, the implant body 400 may be slightlyadvanced along arrows 435 through the introducer 450, opening up theconnecting elements 430 and allowing them to expand and be advancedtoward the target tissue surrounding the target tissue 440. The slidingtubes 410 may not be completely compressing the connecting elements 430.As shown in FIG. 4C, the implant body 400 has completely ejected fromthe introducer 450 and the sliding tubes 410 is advanced to a pointwhere all the connecting elements 430 within each group is fully pressedagainst the target tissue 440, securing each group of connectingelements 430 to the correspondingly desired location on the targettissue 440 and thus fixing/securing the implant body 400 against thetarget tissue 440. The sliding tubes 410 may be flexible or rigid. Allconnecting elements 430 within each group can be interconnected togetheror separately controlled, in order to achieve the desired therapeuticand/or diagnostic outcome(s).

Multiple tissue interfaces, such as electrodes, extending from a singleneuromodulator or from multiple neuromodulators can be positioned in theabove described manner on multiple nerves, nerve bundles, nerve roots,or other neural tissue. Modulation of multiple nerve sites may benecessary for certain applications and therapies. For instance, in orderto treat back pain effectively by completely blocking or masking pain,multiple DRGs, dorsal roots, or nerve bundles at multiple vertebralevels (i.e. T12, L1, L2) and at one or both sides (left and right) canbe modulated. Depending on the affected region, the area of coverage canbe expanded by activating more and more electrodes until the entireaffected region is covered and pain is eliminated, blocked, or masked inits entirety. Unnecessary electrodes will not be activated, savingenergy. The multiple interfaces or electrodes can deliver the samemodulation profile, different modulation profiles, or same modulationprofiles but in a coordinated manner to improve therapeutic outcome andmitigate side effects. This coordination could depend on simultaneous orsequential activation, and may depend on other types of sensed orcollected information. For example, in some applications such as whenmodulating intestines to induce peristalsis, modulation of multiplesites along the intestine at different times but periodically and incoordinated manner with respect to one another is more beneficial toinduce wave-like contractions. Similarly, other therapies may requireinterdependent modulation which can be controlled by a single ormultiple controllers which are aware of each individual implant's orelectrode's scheduled modulation profile. Also, feedback can be used tosense neural, muscular, biological, physical, or other activity, andthis information can inform adjustments to the modulation profile forone or more modulation sites, as shown in FIG. 7. In FIG. 7, five ofseven implanted modulation sites are activated (activated sites 700 a)to completely alleviate pain in a patient. More interfaces or electrodesare implanted than are necessary to avoid multiple implantationprocedures. However, after implantation, specific interfaces orelectrodes can be activated or disabled in order to achieve the desiredtherapeutic effect. The multiple modulation sites may comprise multipledorsal root ganglion sites on different sides and multiple levels. Theselection of which sites to activate and which sites to disable(inactive sites 700 b) can be performed by relying on patient feedbackin an iterative approach or by sensing and controlling activation in aclosed-loop manner.

It may be clinically advantageous for the modulation interfacecomponents to be flexible and soft in order to prevent tissue irritationdue to its motion, which can result from physical activity or othercauses. Metal or other rigid material electrodes are generally not softenough compared to the surrounding tissue and may cause such irritationand inflammation. This, however, may have to be accomplished withminimal compromise to electrode conductivity and not cause significantdegradation in electrode/tissue impedance which would lead to increasedpower consumption. Soft electrodes can be implemented on flexible,biocompatible printed circuit substrates. In order to reduceelectrode/tissue impedance, planar contacts can be implemented of adesired size to accommodate target tissue stimulation. For example, manynerves or nerve ganglia may be on the order of a few millimeters indiameter. Therefore, in order to stimulated the desired ganglion andprevent stimulation of adjacent tissue, the electrode size may be setsomewhere on the order of 0.5 mm to 2 mm in diameter. Furthermore, theseelectrodes can be electroplated or coated with Pt—Pt, Ir, Au, Pt-blackor other similar coatings in order to increase effective surface area ofthe electrode and reduce its interface impedance. Furthermore, multiplecontacts (electrode pads) can be spread around the flexible substrate toimprove versatility. These electrode pads can be hard wired (connectedin a certain configuration) or can have programmable connections whichcan be utilized to create current steering and improve therapeuticresults. Various flexible substrate electrodes and their securingmechanisms and devices are shown in FIG. 14, FIG. 15, FIG. 16, FIG. 17,FIG. 18, and FIG. 19 as further described below and herein. These mayinclude electrodes which can wrap around target nerves or tissue and canbe anchored to the desired tissue using pins, screw-like structures, orany other attachment method. Furthermore, anchoring pins can beelectrically connected to the electrodes and can be conductive. Thisway, if anchoring pins are passing through nerve tissue, current can beconducted from the pins (inside the nerve tissue) to an oppositepolarity electrode pad which can be located on the outside of the nerve.Structures which are not implemented on flexible substrates can still bemade softer by coating them with softer biocompatible materials such assilicone prior to implantation. The electrode can be left uncoated orcan be coated with conductive materials.

Flexible modulation interfaces may be difficult to guide duringimplantation procedure because of their compressible or otherwiseadjustable geometry. In order to make implantation procedure easier, oneor more electrodes comprising at least one flexible portion can first beattached to and/or within a rigid or semi-rigid structure, such as acannula, catheter, or lead, which can be used to advance and navigatethe one or more electrodes to the desired location. Once the electrodesare in proximity of the target location, the host rigid or semi-rigidlead can be detached and extracted, leaving behind only the one or moreelectrodes.

Electrodes can further be coated with drug eluting agents in order toprevent or otherwise reduce inflammation, infection, pain, and/or otheradverse effects. The agents may include analgesics, anesthetics,antibiotics, antiseptics, steroids, anti-inflammatory drugs, collagen,pharmaceuticals, and/or other agents with beneficial effects. Examplesmay include ibuprofen, bupivacaine, lidocaine, maprivacaine, procaine,dexamethasone, betamethasone, and epinephrine. Some applicableantibiotics or antiseptics could include vancomycin or cefalozin. Otheragents may be suitable for use in other cases, so this list is notexhaustive.

Using the electrodes and other components of the present invention,nerve bundles and/or ganglia can be relatively simple to target whenplacing electrodes for nerve modulation. For example, dorsal rootganglion can be located with the assistance of common imagingmodalities, such as fluoroscopy, by referencing nearby bone structuresand landmarks, such as vertebral foramen 505, spinous or transverseprocess 510, vertebral arch 515, lamina 520, superior articular process525, or pedicle 530, as shown in FIG. 5. The position of the dorsal rootand dorsal root ganglion with respect to these landmark structures doesnot vary significantly from patient to patient. Therefore, thesestructures may provide an easy way to guide positioning of theelectrodes and other components of the present invention using commonimaging modalities. Further relevant structures include the spinousprocess 535 and the vertebral body or centrum 540.

The majority of existing neurostimulation treatments rely onelectrically activating nerves, and this activation has been effectivein a variety of treatments. The behavior of neurons and tissues areoften directly influenced by electric currents and voltages, so this isa straightforward way of interacting with these types of tissues.Controlling the parameters of the applied current and voltage can offeradditional flexibility and control of the physiological responses. Forsome nerves, applying electrical modulation at high frequencies canblock transmissions, and this modulation can be very effective inmanaging certain types of pain. Other types of tissue, including smoothmuscle, may require modulation pulse widths greater than 2 ms in lengthto have an effect, and these can be applied with a certain duty cycleand duration. For some patients, high amplitude stimulation may benecessary to have the desired effect. This could be due to a number offactors, including variations in tissue impedance, differences inphysiological structure, or differences in the placement of themodulation system. Localizing the placement of the modulation site canreduce energy requirements for inducing the desired physiologicalresponses because less energy is wasted in surrounding tissues. In somecases, smaller electrodes can result in increased impedance at thetissue interface, which can increase the requirements of electricalmodulation. This requirement can be mitigated by coating the electrodeswith certain materials. In particular, platinum or platinum-iridiumcoatings or the other previously described coatings are non-toxic andhave been shown to dramatically reduce this impedance for several typesof modulation systems. Other materials may be advantageous depending onthe tissue type and the desired type of modulation. Charge balancing thedelivered current can be included because it can reduce voltage andtherefore reduce power requirements, and it can minimize adverseeffects. There can be numerous methods for balancing charge, andneuromodulation requiring high duty cycles can require sophisticatedcharge-balancing methods. Charge balancing can be accomplished withelectronic circuits that precisely measure delivered current and/orvoltage at the interface and use feedback control to properly adjust oneor more stimulation parameters. Other methods can intrinsically orpassively balance the delivered current in the way current reacts tochanges in the applied voltage.

For many applications, alternatives to electrical modulation that canoffer significant advantages. Research has shown that mechanical forcesor vibrations at nerves or other tissues can induce physiologicaleffects similar to electrical modulation. For most types of tissue,generating mechanical forces can be more power efficient (e.g. becauseof the relatively high electrical impedances of tissue encounteredduring electrical stimulation). There can be several ways thesemechanical forces can be induced by the apparatus of the presentinvention. Electromagnetic actuators can be used with either internal orexternal magnetic fields. These systems may be very power efficient inconverting electrical to mechanical energy and function similar tomotors. Alternatively or in combination, ultrasonic or other mechanicalvibrations can be applied to the tissue directly or to a device with adesired resonance, causing it to vibrate at the desired location. Othermethods involve activating nerves with electric or magnetic fields,which can be generated either internal or external to the body. Theseactuators or devices can be miniaturized and used with similarattachment methods as described herein.

The modulation system of the present invention can monitor impedance orother aspects of the quality of the connection to tissue during and/oroutside of stimulation, in order to keep track of the electrode/tissueinterface status and electrode status to ensure the contact with tissueremains acceptable. The impedance can be monitored by driving currentthrough tissue and measuring voltage across a known resistor value whichis placed in series with electrodes, thus measuring the amplitude ofstimulation current, and by measuring the voltage difference between theelectrodes. The magnitude of impedance can be calculated from themeasured values of stimulation current and voltage. Additionally,relative phase of current can be measured with respect to voltage phasefor a given applied stimulation tone to derive the phase of impedance.Alternatively or in combination, the delay between applied voltage andcurrent can be measured to derive the phase information.

Methods for sensing different types of information (e.g. patientinformation or apparatus information) can also greatly improve bothdiagnostics and therapies. These types of information include but arenot limited to action potentials, neural activity, muscular activity,and other biological, chemical, biochemical, or physiological signals.Electrical activity can be sensed through electrodes at or near the siteof interest. There are a variety of known sensors that can detectpressure, chemicals, pH, and other phenomena that may be of interest andmay be incorporated into the systems and devices of the presentdisclosure. Additionally, information from other areas of the body ordirectly from the patient can be incorporated into the diagnostic ortherapy. This information can adapt modulation parameters used onspecific nerves or tissues, or it can activate or deactivate certainmodulation sites for therapies involving multiple sites. For chronicconditions, the severity can vary and the treatment can adapt to thisseverity to treat as necessary. Also, it can adapt to changes in thecondition or the patient to continue delivering effective treatment.This information can also be used to track the progress of the conditionand the treatment, and to keep caretakers informed and to allow them touse their expertise to adjust the treatment if it is needed.

These new methods for modulating, sensing, and/or controlling thetherapy or diagnostics can be accomplished with apparatus of the presentinvention, such as using minimally invasive devices with wireless powertransfer and communications. Pulse generation can be done locally on thedevice or externally transmitted through a transmission system. Theimplantable devices can also include local energy storage, such asbatteries or capacitors. If a more traditional system is used, the newattachment systems and modulation interfaces would allow for preciselylocating modulation sites and operating with multiple sites. Inparticular, different devices may be most suitable for certainapplications, and the methods described herein can operate withdifferent types of devices, tissues, or locations within the body.

Referring to FIG. 6, spinal nerves may be stimulated to treat pain. Thedorsal root ganglion DRG and the dorsal root DR are shown in FIG. 6.Electrodes or other interfaces can be used to delivery energy tomodulate the DRG and/or the DR in order to suppress and/or mask pain.Depending on the selected modulation profile, the propagation of neuralactivity with pain information can be blocked from the brain ormodulation can cause paresthesia (tingling sensation), which can beeffectively used to mask pain. Both nerve sites, the DRG and the DR, mayprovide a simple way to target electrode or interface placement andanchoring, and may be effective locations at which to deliver energy tocause desired therapeutic effect(s).

Referring to FIG. 8, attached electrodes or other interfaces are shown.These attached electrodes or other interfaces may be positioned arounddifferent nerves and nerve bundles and to neuromodulator implants whichare shown schematically. For example, there may be sets 801 and 802 offour connections to two different dorsal root ganglions, a set 803 ofthree connections to a dorsal root, a set 804 of attachments with threeconnections with a fourth center-connection inside the bundle positionedon a peripheral nerve ganglion, a set 805 of attachments with twoconnections to a dorsal root ganglion. One or more of the connectionsmay be provided with center needle-like electrode may penetrate insidethe peripheral nerve bundle and may act as one of the terminals forsinking or sourcing current.

Referring to FIG. 14, embodiments of the present disclosure may providea flexible interface 1400 comprising flexible interface electrodes 1410implemented on a flexible printed substrate 1420. The flexible substrate1420 can split and can have multiple interface sites which would beconnected to a therapeutic or diagnostic device. For neuromodulation,the conductive electrodes 1410 may form electrical connections withtissue directly be being in proximity or in contact with it or throughconductive pins 1430 which may pass through conductive holes 1440 andthrough target tissue, securing the electrodes to the tissue.

Referring to FIG. 15, embodiments of the present disclosure may provideanother flexible interface 1500 attached to target tissue 1510 (such asa nerve bundle) using pins 1520. The pins 1520 can be inserted throughtarget tissue and into receiving holes or starting from holes and thenthrough the target tissue 1510. The securing function or anchoring ofthe pin 1520 can be achieved by utilizing a nut or matching plate 1530(similar to the head of the pin). The nut 1530 can mate with the pin1520 and secure the pin 1520 and flexible substrate 1540 of the flexibleinterface 1500 in place. Conducting pins 1520 can be used to sense orstimulate target tissue from the inside when preferable.

Referring to FIG. 16, several different pin configurations for securinginterfaces to target tissue are shown. A pin 1610 may be pre-split andmay split open after passing through the desired tissue and interfacereceptacle, thus securing/anchoring the interface to the target tissue.The split end of the pin 1610 may be beat to secure the pin 1610 inplace. One or more bending pieces 1625 can be on the end of a pin 1620.For example, the bending pieces may comprise a nut or similar componentthat can be used to secure the pin 1620 and to ensure that the beat pincan press through a larger surface area. The pins 1610 and 1620 may benail-like. Screw-like pins 1630 may be used to screw into tissue and/orthrough a mating nut or receptacle on an interface electrode. The pins1610, 1620, and/or 1630 may be conductive.

Referring to FIG. 17, a flexible interface substrate 1700 is shown. Theflexible interface substrate 1700 may comprise multipletissue-connections and anchoring mechanisms utilizing pins or screws1710 to secure to target tissue. Secured pins 1710 a and unsecured pins1710 b are shown by FIG. 17.

Referring to FIG. 18, flexible interfaces 1800 which can wrap aroundtarget tissue such as nerves are shown. The flexible substrate 1820 ofthe flexible interfaces 1800 can have conductive wires or electrodes1815 which may be partially insulated from tissue and may connectelectrode plates, pads, or other exposed conductive tissue interfaces1810 to a pulse generator, sensing interface, modulation interface, orother therapeutic and/or diagnostic device. The flexible interfaces 1800can have one or more mating terminals 1830 which can be used to securethem by connection after one end is wrapped around the target tissue.This would lock the electrode in the desired wrapped position. Multiplemating terminals can be used to provide flexibility to accommodatemultiple target tissue sites. Some examples of mating terminals arematerials such as Velcro™, mating pins and holes, and two holes whichcan be secured with a wire or thread. A T-shaped flexible substrate canbe used instead of an L-shaped substrate. Also, cascaded T- or L-shapedextensions (e.g., leaves) can be branching out from the main lead (root)when multiple similar attachments may be necessary.

Referring to FIG. 19, a wrap-around flexible interface 1900 can besecured through pins or screws which can pass through tissue. FIG. 19shows the flexible interface 1900 in its unwrapped configuration 1900 aand its wrapped configuration 1900 b.

Implantable devices may be limited in their design by the power budget(e.g. short-term or long term power requirements), which can restrictboth miniaturization and functionality. Neuromodulation devices canrequire significant power to provide therapy because of the relativelyhigh voltage and current requirements needed to drive stimulation. Forfully wireless devices, the power limitation is typically the designconstraint and limits the performance of the device. The envisionedusage of embodiment of the present disclosure is shown in FIG. 20. FIG.20 shows one or more implantable devices 2010 controlled and poweredfrom external device 2030 external to the body BD. The elements of theoverall system 2000 can allow for mm and sub-mm neuromodulators whileoffering the flexibility to operate with different therapies and fordifferent applications. This miniaturization can be accomplished in partby the ability of the overall system 2000 to interface with differentantennas and the on-board intelligent power management system. Theexternal device 2030 may include components for power transfer, datatransfer, programmability, data management (including processing andvisualization) and a user interface for doctors and/or patients, such asa handheld interface 2020. The implantable device 2010 may be implantedminimally invasively and may receive power and data from the externaldevice 2030. The delivery of the implantable device 2010 may be througha needle, an endoscope, or with many other methods. The implantablesystem may be delivered to any of a variety of implantation sites asdescribed herein to perform neuromodulation therapy or diagnostics. Asystem diagram of embodiments of the implantable device 2010 is shown inFIG. 21 and an external device 2030 is shown in FIG. 22. The externaldevice 2030 may include a transmission antenna 2210 that can be placednear the surface of the skin in close proximity to the antenna 2110 ofthe implantable device 2010. This link can transfer both power and datato the implantable device 2010. The external device 2030 can alsoreceive information from the implantable device 2010 via several methodsdepending on the data protocols of the implantable device 2010. Thiscommunication may include a load modulation sub-system in which antennaimpedances are sensed, or tissue conduction in which small electricalsignals are transferred through the tissue itself. The external device2030 can operate with either batteries or with a wall outlet. Theexternal device 2030 may also have a separate communication protocol2220, such as Bluetooth, for interfacing with computers, smart phones,or other devices. The external device 2030 can include an informationdisplay with information about the device performance, information aboutthe therapy, or controls for adapting parameters. Data can betransferred at speeds up to and exceeding 20 Mbps to accommodateconfiguration and control of the device 2030 as well as real-timetreatment adjustments, such as between 0.1 and 20 Mbps, or between 0.5and 4 Mbps. Data and power can also be transferred to multiple devicessimultaneously and the high-speed of communication allows for severaldevices to adapt and adjust in real-time. Sensors can be incorporatedwith the external device 2030 and also make use of the high-speedcommunication system for diagnostics or real-time feedback ofphysiological parameters to inform the doctor or patient of thefunctionality of the device or to provide feedback to the system toadapt the treatment. This information can be stored locally ortransferred securely to other devices or to the cloud where it isaccessible from the internet. Data processing and visualization can alsobe performed locally or on other devices.

The external device 2030 can wirelessly power implantable devices 2010via either electromagnetic coupling or through a mechanical transfer,such as via an ultrasonic signal. Depending on the application, patient,frequency, number of implants, depth of implants, and other factors, theexternal device 2030 can operate with a variety of antennas ortransmitters of different sizes. The external device 2030 can interfacewith one or more antennas via RF signal generation and conditioningcircuits and matching network which can accommodate a variety of suchantennas and operating frequencies. Moreover, the external device 2030can adjust how much power is transferred to one or more implantabledevices 2010 based on feedback from the implants and/or based onexternally sensed quantities, such as tissue and system temperature.

For wireless powering and communication using electromagnetic energy theexternal device 2030 uses one or more antennas 2210. The one or moreantennas 2210 can be implemented on a printed circuit board comprisingone or more rigid and/or flexible substrates. Alternatively, textilesubstrates can be used to implement one or more such antennas. Also,multiple external antennas 2210 can be used simultaneously orexclusively in order to provide better coupling between the implantableand external antennas 2110, 2220.

High-speed, efficient communication can be accomplished by combiningdata transfer into the power signal. This combination can benon-trivial, especially at high frequencies because most modulationmethods can have a significant effect on power transfer and using aseparate communication system would result in large interference.Asynchronous methods can dramatically reduce system requirements, andpower transfer can remain uninterrupted by employing methods thatminimally modulate the amplitude. These data transfer methods could alsooperate with multiple devices simultaneously by assigning each device aspecific address or ID. The communication methods described can useencoding and encryption to improve reliability, safety, and security.

The external device 2030 can rely on data from the implantable device2010 for multiple purposes. These purposes include improved positioningof the external device 2030 to improve coupling between external andimplant antennas 2110, 2120, monitoring of various sensed quantities bythe implantable device 2010, monitoring of implant status and therapystatus. One or more of these sets of data can be used to re-adjust thetherapy either in closed-loop or via user input. The reverse data linkfrom the implantable device 2010 to the external device 2030 can benon-trivial and can be accomplished via a variety of methods. Somemethods may rely on backscattering signal transmitted by the externaldevice(s) to the implantable device(s) by modulating load on the implantantenna. Other methods may rely on implantable device 2010 having atransmitter circuit which generates a carrier signal and transmits it tothe external device 2030. Other methods may include implantable device2010 relying on volume conduction to communicate with the externaldevice by modulating voltage or current through electrodes connected totissue. Depending on the selected communication scheme, the externaldevice can be configured to receive and demodulate this signal from oneor more implants.

The external device 2030 may also keep track of the desired therapyprogram and actual applied therapy to the patient. The external device2030 can collect data from embedded sensors, patient input, and/or oneor more implants, and store the data in embedded memory and/or upload itto external storage such as phone or cloud storage system. The externaldevice 2030 can also issue some one or more notifications to thepatient, doctor, or even emergency dispatch personnel, based on thissensed and stored data.

Treatment parameters can be controlled remotely via the external device2030 and adapted based on performance or changes in the condition. Theexternal device 2030 can be controlled by a doctor, the patient, or somecombination of the two depending on the intended use. Therefore, theoverall device 2000 can accommodate a variety of interface with externalinfrastructure via existing protocols such as Bluetooth, ZigBee, WiFi,2net platform interface, and other wireless and wired general or medicalprotocols and interfaces. These interfaces can rely on built-inencryption or privacy or can incorporate additional custom encryptionand error detection and correction encoding.

Other aspects of the external device 2030 are also described herein,such as form factor, user interface features, compliance features,energy storage and recharging, safety, reliability, privacy, and others.

Referring to FIG. 21, the implantable device 2010 may further comprisean integrated circuit 2120 and an energy storage unit 2130 (such as abattery) coupled to the integrated circuit 2120. The integrated circuit2120 may comprise a power management sub-system 2140 coupled to theenergy storage unit 2130, an implant controller 2150 coupled to thepower management sub-system 2140, a sensor interface 2160 coupled to theimplant controller 2150, an electrode or lead interface 2170, a pulsegenerator 2180 coupled to the implant controller 2150 and the electrodeor lead interface 2170, and a transceiver 2190 coupled to the antenna2110, the power management sub-system 2140, and the implant controller2150.

Referring to FIG. 22, the external device 2030 may further comprise atissue interface 2230 which may comprise the antenna 2210 and skincontacts 2240. The external device 2030 may further comprise a powersupply 2250, a system controller and memory 2260 which may be coupled toa Bluetooth or other standard communication protocol 2220, a transceiver2270 coupled to the system controller and memory 2260, and a signalconditioner and multiplexer 2280 coupled to the transceiver 2270 and thesystem controller and memory 2260.

Several applications and their preferred embodiments are described asfollows.

The physical form of the external device 2030 could take a variety offorms depending on the intended application, the location of theimplantable device 2010, and the included features. This form could be asingle component or could have multiple components as well, such asseparating the transmission antenna from the battery pack and userinterface. The size of the antenna 2210 can be determined by theoperating frequency, implant depth, and the antenna used in theimplantable device 2010. These antennas 2210 can be loops, patterns, orpatches on the order of several cm on a side. The external device 2030can have the ability to interface with a variety of antennas 2210 inorder to increase its flexibility for use in different applications. Insome embodiments, there is a common connector to each of these differentantennas 2210 and the primary external device 2030 has the necessarycomponents (e.g., the signal conditioner and multiplexer 2280) to shiftfrequencies, power levels, and matching systems or sub-systems tooperate with these different devices. The primary external device 2030may incorporate the power source 2250 and user interface along withelectronic components for data communication, management, storage,processing, and visualization. This external device 2030 will likely bedominated by the size of the battery, though should be on the order of˜cm in each dimension.

The external device 2030 can be encased in a single enclosure ormultiple enclosures. FIGS. 23a-23d depicts several methods of operationfor these devices and methods for networking them with a user interfacesuch as a handheld interface 2020. The enclosure with the antenna 2210should be placed close to the surface of the skin, and may also includeelectrical contacts 2240 (e.g., electrodes) with the skin for detectingbiological parameters or receiving certain types of information for theimplantable device(s). These contacts 2240 can also transmit informationto one or more implantable devices 2010 or deliver therapy through bodyconduction. This antenna enclosure may be incorporated into articles ofclothing such as shirts, belts, hats, or other clothing, or it may be aseparate system or device adhered to the skin directly. The electroniccomponents for communication, data systems, and user interface shouldalso be enclosed either separately or together with the antenna. Thisenclosure could be constructed in a way to fit in a pocket or attach toa belt. The external device 2030 can also take a form factor of aself-adhesive patch, which can be placed over the implant. This formfactor is depicted in FIG. 26. It can be implemented on a flexiblesubstrate 2610 (e.g., a substrate comprising one or more flexibleportions) and can include a battery and other circuitry 2630, adhesivessuch as an adhesive layer 2620, gels, matching gels for eitherconduction electrodes, antenna, or both. Gels or pads can also be usedto control the separation distance between the antenna and tissue or toremove heat generated due to power transmission. These patches can alsobe connected to other patches and/or to a handheld controller viatethered (wired) methods or wirelessly. Tethered methods can useflexible cables, e-textiles, or other cables or wires to provide thepower and/or data link.

Referring to FIGS. 23a -23 d, the handheld interface 2020 may networkand tether with multiple external devices. As shown in FIG. 23a , thehandheld interface 2020 may communicate wirelessly with two or moreexternal devices 2030 which may communicate wirelessly with one another.As shown in FIG. 23b , the handheld interface 2020 may communicate withan external device 2030 through a wired connection. As shown in FIG. 23c, the handheld interface 202 may through a wireless connectioncommunicate with multiple external devices 2030 which may communicatewith each other either wirelessly and/or with a wired connection. Asshown in FIG. 24c , the handheld interface 2020 may communicate througha wired connection with multiple external devices 2030, each of whichmay in turn communicate with each other either wirelessly or with awired connection.

To transfer energy to the implantable device 2010, an external antennacan be placed in close proximity to the surface of the skin. Thisplacement can be accomplished by incorporating the antenna into one ormore articles of clothing or with a separately adhered device such as apatch. This external antenna can be enclosed with the power source orattached via wires to an enclosed device with batteries and otherelectronics. The size of the external antenna varies with the size ofthe antenna on the implant, though the external antenna size istypically several cm on a side and a few mm thick. This patch couldinclude additional sensors or electrical contacts to the skin to enhancethe features of the overall system. The antenna can collect informationfrom the implant or from its electrical connections and store it orcommunicate it to other devices.

The frequency of power and data transfer can be tuned to one or morespecific implants, and this tuning may require adjusting the externalantenna or by adapting the matching circuitry at the input of theantenna itself. Variations in implant location and environment couldalter the optimal frequency and this frequency alteration would requireadaptations to the matching devices in place. This matching could beaccomplished with either discrete or distributed components, and couldbe adjusted after the implant is placed inside the body. In someembodiments, the external antenna is designed to operate specificallywith one or more implanted antennas. Based on the characteristics of theantennas, it is possible to design either passive matching circuitry oractive matching circuitry. In some embodiments, the matching isaccomplished passively with inductance and capacitance at the input ofthe antenna and tuned to the specific frequency of the implant. Thismatching can also be made adaptive by digitally switching in differentamounts of capacitance to optimize the setup. If the external antenna isalso a receiver for data communications, there can be additional RFcomponents for improving sensitivity and decoupling the transmittedsignal and the received signal.

The external device 2030 may transfer power to the implantable device2010 through the tissue, and can use any of a number of power transfermethods including electromagnetic or mechanical techniques. Ultrasonicpowering may involve transmitting high frequency sound waves throughtissue (e.g. to be received by piezoelectrics of the implant).Ultrasonic energy has minimal attenuation when traveling through mosttissue environments though significant reflection at air or boneinterfaces can occur. This ultrasonic power transfer method may alsorequire good contact with the skin, which may include placement of gelat the interface of the transmitter and the skin. Powering can also beaccomplished with electromagnetic power transfer as described withregard to FIG. 24, in which electric and/or magnetic fields are alteredand the energy in these changing fields is captured through receivers(e.g. inductive coils) on the implant. Attenuation of this energydepends on the frequency and the types of fields transmitted, and theattenuation can be significant for deeply implanted devices. In someembodiments, the implantable device 2010 is powered through RF signalsin the low GHz range or high MHz range. This frequency range can allowfor very small antennas at the receiver that are capable of receivingsufficient energy for diagnostics or therapeutics. Power transfer can beadapted based on the quality of the transmission link. In someembodiments, data can also be modulated on the power carrier. There arealso set safety limits of tissue absorption (Specific Absorption Rate(SAR) and other similar constraints) which must be adhered to for use inmedical applications. An additional safety consideration is in theheating of the external device itself, which results from powertransmission and other functions. Guidelines about heat should beadhered to in the design of the final overall system and may limit powertransfer in some circumstances. Additionally, guidelines from the FCCshould also be adhered to, which will most likely require operation inthe industrial, scientific, and medical (ISM) frequency bands.

One or more external device antennas 2210 and/or one or more implantableantennas 2110 can utilize link gain optimization techniques usingvarious improvement methods. Some of the improvement methods mayinclude: mechanical positioners; energy focusing techniques, such asbeam steering used in far field regions, mid-field energy (power)focusing by generating optimal equivalent currents that focus energyspatially inside tissue; mid-field or near-field focusing by utilizingmultiple phase and amplitude adjustable sources or antennas to shapeelectromagnetic fields inside tissue to achieve focusing and spatialfocus steering. Other techniques such as electromagnetic lenses,metamaterials, left-handed materials, phase-adjustable materials, andother similar methods can also improve the link gain or optimize powertransfer through better control the electromagnetic energy. Furthermore,conducting elements within the antennas 2110, 2210 can be adjusted tocontrol focusing or improve link gain dynamically.

These methods can be accomplished in real time using feedback signalsdescribed in sections for power and link gain adjustments. Theseoptimizations or adjustments can be done with an open loop or closedloop method as needed. They may be a need for these methods only onceafter implantation, periodically, on-demand, or continuously.

Alignment of antennas can be guided through active methods described inalgorithms for positioning, or can utilize more passive or semi-activealignment methods, such as using magnets to align antennas, mechanicalprotrusions, or electromagnets. The alignment can also be assisted withinformation about the link from the transmitter and/or the implant.

Power transfer can be combined with data transfer to increase efficiencyand reduce system overhead. This can be accomplished with small changesin the amplitude of the power transfer signal that can be detectedasynchronously at the implanted receiver. Potential methods of combiningdata transfer to the implant are described in later sections, and thepreferred method is described in detail.

The external device 2030 can be powered through batteries or with directconnections to wall outlets. Batteries allow for portable systems andfor most applications should operate for several days before requiringrecharging. Some applications may be more power intensive and requiremore frequent recharging. As an additional feature, the system canoperate from wall outlets when the patient is at home or in a placewhere this is convenient. The power source can be located in a separateenclosure from the antenna 2210 to increase the comfort of the overallsystem. The antenna should be located in close proximity the implantabledevice, and the battery pack could significantly increase its size andweight, and the ability to carry it in a different location could reducepatient discomfort. Referring to FIG. 25, the external device 2030 maycomprise a swappable rechargeable battery 2510 to power the externaldevice 2030. Each external device of the external device 2030 may beprovided with one or more swappable rechargeable batteries 2510.

There is a two-way communication link between the implantedneuromodulator and the external transmitter. The forward transmissionfrom the external antenna to the implantable device 2010 may provideinformation for the controller to configure the operation of the device,and can operate at speeds up to and in excess of 20 Mbps. Many forms ofmodulation can be used including both amplitude and frequencymodulation, however combining data with power transmission introducesadditional challenges. Conventional forms of data modulation cansignificantly impact the amount of power transferred, and trying to usemultiple antennas or different frequencies would need to contend withlarge levels of interference from the power carrier. Another moreindirect method is for the external device 2030 to have electricalcontact with the surface of the skin and transmit small electricalsignals through the tissue. In some embodiments, the communication linkis combined with the power transfer link in a way that minimizes theeffect on power transfer, and operates asynchronously to reduce theoverhead on the chip. This method could function very similarly to whatis described in U.S. Pub. No. 2013/0215979 (the contents of which areincorporated herein by reference), which uses amplitude shift-keyingwith data encoded in the pulse-width (ASK-PW). In this method, theamplitude of the power carrier is modulated with minimal depth, whichminimizes the impact on power delivery to the device as desired. Datacan be encoded in the width of transmitted pulses, allowing forasynchronous operation on the implant, which reduces the complexity ofthe on-chip circuitry. By eliminating the need for carriersynchronization circuitry, the power consumption on the implant is alsominimized. This method can also easily accommodate variable data ratesand modulation depth, which gives flexibility in its overall powerconsumption and also can increase robustness when the antenna link isweaker. A high-level diagram of this method is shown by the operationaldiagram 2900 in FIG. 29. An envelope detector may extract the envelopeof the power carrier, and the resulting signal is converted to afull-swing digital signal. The envelope detector uses a dynamicreference to extract the desired signal because of the inherentfluctuations from wireless powering, and the operation of this system.The digital signal has both long and short pulses that were recoveredfrom envelope of the power carrier, and these pulses are integrated todetermine the encoded data. The falling edge of the pulse can be used toclock the data as shown in the figure, and this clock signal can berepurposed for other uses on the chip as well. The diagram 3000 in FIG.30 also depicts the waveforms of the signals, showing the transmittedenvelope, the digital version of the envelope, and the method forextracting data from the pulse width. An alternative to this approach isshown by the circuit diagrams 3100 in FIG. 31, in which multi-levelencoding is used for data. This method can allows for a constant clockperiod in transmission, simplifies dynamic reference settings, and has amore constant average power transmitted.

One way to generate ASK-PW signal to power the implant and send data toit is to first generate a carrier signal, then encode data on it bymodulating the amplitude of the carrier signal. The modulated carriercan then be bandpass filtered and amplified to generate desired spectrumand amplitude prior to transmission. The baseband data waveform whichmodulates the carrier signal can be conditioned prior to mixing it witha carrier signal to achieve desired pulse shapes and spectrum. Varietyof pulse shaping techniques can be used to improve signal integrity ofthe communications. Pulse shaping can be achieved using analog ordigital methods. For example, low pass filter can be used as an analogmethod or digital. Alternatively, baseband data stream can be generatedusing a digital waveform and then converted to analog signal using aDAC. The modulated RF carrier can also be generated directly using ahigh speed DAC. In other embodiments, modulation of a carrier signal canbe achieved by loading a transmission line with a transistor or asimilar controllable component which can modulate impedance of thetransmission line through which the signal from carrier generationcircuit passes. The baseband data can connect to the control terminalsuch as gate terminal on a FET transistor or a base terminal on a BJTtransistor. This way, the baseband data modulates the impedance of thetransmission line, and therefore, the reflection and transmissioncoefficients, which directly affect amplitude of the carrier signal. Theresulting modulated carrier signal can then be conditioned and amplifiedfor transmission to the implant. The baseband data can be analog ordigital waveform in the above described method. Digital data stream ispreferred because it is easier to decode on the implant when usingASK-PW. Data is encoded in pulse width of the modulating signal.Amplitude modulation depth or modulating index can be adjusted bycontrolling the bias voltage of the modulating transistor as shown inFIG. 31. Modulation depth can be controlled by adjustingcollector-emitter bias voltage on the transistor. The baseband data canbe driven by FPGA and resistors R1 and R2 attenuate the signal to theproper level to control the BJT transistor. A large DC block capacitorand a choke inductor are implemented to bias the transistor withoutinterfering with the RF signal. Carrier signal of desired frequency canbe generated using well known methods such as voltage controlledoscillator (VCO) or digitally controlled oscillator (DCO). In order toachieve specific carrier frequency, a crystal oscillator can be used forreference frequency in a phase or frequency locked loop (PLL). Numerousmethods can be used to generate the carrier signal.

The reverse data transfer from the implantable device to the externaldevice(s) will operate in conjunction with the forward link, and will becapable of data transmission speeds up to and exceeding 2 Mbps, such as0.1-1 Mbps. It is possible to have an oscillator on-chip for an activetransmitter that sends data back to external transmitter. This wouldrequire significant power on the implant to operate and would need tocontend with interference from the power carrier. Even with thesechallenges, these implementations may have advantages in certainsituations. Other methods require much less power on the chip, and areadvantageous in many situations because of the power limitations of theimplantable device. One potential method with a minimal power budget isthrough a backscattering link, in which the loading at the antenna ofthe implant is altered to introduce mismatch, which can then be sensedat the transmitting antenna. This method is similar to what is used inRFID systems, though transmitting through tissue poses a different setof challenges. This method can be sensitive as the environment changes,and variations are common when operating in tissue. To mitigate theeffects of the operating environment, several possible loads can beimplemented, and the load that maximizes the received signal can beused. This load satisfies two requirements: maximizing the averagebackscattered power per bit (max{σ₁+σ₂}) and maximizing the Euclideandistance between the reflection coefficients on the Smith chartcorresponding to the matched and mismatched loads (max{|r₁−r_(2,k)|}).In this description, σ corresponds to the termination-dependent implantantenna radar cross-section and r are the reflection coefficientscorresponding to matched termination and terminated with some load, k.In order to demodulate such signal, direct conversion receiverarchitecture can be implemented on the external device, as shown in thediagram 3200 of FIG. 32.

The external reader may comprise transmit and receive signal paths whichare isolated by circulator as shown in FIG. 32. The transmit signal pathmay comprise a power carrier generator which connects to directionalcoupler whose through port is connected to ASK modulator. The data maybe configured on an FPGA and modulates the power carrier with adjustablemodulation depth, ranging between 0 and 100%. The modulated powercarrier can then be filtered with 80 MHz bandpass filter around thecarrier and can be fed to a power amplifier. The power amplifier mayamplify the signal to sufficient power level to provide enough power tothe implantable device, which could be between 20 and 36 dBm, dependingon chip power consumption requirements, implant environment, andseparation distance and medium between the external and implantantennas. The external reader and the implantable device are coupledthrough a pair of weakly coupled antennas.

As was mentioned earlier, the receive signal path can be isolated with acirculator that provides isolation between the forward and reversesignals of approximately 20-30 dB. However, because the backscatteredsignal is significantly lower power than the transmit signal, the 20 dBof isolation is not always sufficient to suppress the leaked powercarrier and ensure that the amplifier in the receive signal path doesnot saturate. In those cases, active blocker rejection techniques can beused to further suppress self-interference. Additionally, forward datalink modulates the carrier, which causes significant fluctuation incarrier amplitude, further complicating signal processing in the reversedata recovery. Therefore, a duplex switch can be implemented in thereceive chain which provides additional 60 dB of isolation during thetransmission of the forward data. Because the receive path in this caseis implemented using only the in-phase component, it is also importantto synchronize the phases of the RF and LO signals at the mixer.Therefore, a passive phase shifter can be implemented to ensure that thesignals are in phase. There can be an additional amplifier for the LOsignal to ensure that LO signal level is in appropriate amplitude rangebetween 7 and 13 dBm for proper mixer operation. The mixer output canthen be filtered by a low pass filter to eliminate undesired highfrequency components and can be amplified before decoding the data.

Another method for reverse communication uses the stimulation electrodesto transmit a small signal through the tissue. Here, the external device2030 may require some form of electrical connection with the surface ofthe skin to detect the small fluctuations in electrical stimulation.This has potential advantages in that it requires very low-power fromthe implant, and can operate at frequencies where there won't beinterference with the forward link. Additionally, it can operateasynchronously and simultaneously with forward data transfer, whereasbackscattering modulation and active transmission through the antennawould be very limited in this type of simultaneous operation. Becausethere is little or no interference, the external device can have a verysensitive receiver, which means that the electrical signals sent throughthe tissue can be very small (even below <1% or below 10% of thedelivered therapeutic stimulation). If there are multiple devices, thismethod would allow for rapid communication between the devices and theexternal device.

In order to demodulate signal which is transferred using volumeconduction from the implantable device to the external device, theexternal device can use one or more electrodes or electrode pairs whichare in contact with tissue. The electrodes could detect the voltagesgenerated by the implant and feed these signals to the readoutinterface. One possible embodiment of sensor interface AFEimplementation is shown in the diagram 3300 of FIG. 33. In the FIG. 33,the sensor interface may comprise electrodes connected to tissue whichact as a transducer from ionic or electronic current flow in tissue to avoltage difference which can be further sampled and processed by analogfront end (AFE) of the implantable device. AC-coupling block couldconnect to the electrodes and filters out undesirable low frequencycontent of the sensed signal. Low noise amplifier may amplify thesampled signal to a desired amplitude so that the signal can further befiltered out by the low pass filter. There may be an additionalamplifier after the filter. The analog signal at the output of low passfilter may then be converted to digital signal using analog to digitalconverter. The sampling frequency and resolution may be based on thedesired application and data rate. One or more of the parameters of theAFE can be made controllable to make the device versatile for a varietyof applications and compatible with a variety of transducers. Forexample, the high pass filter and low pass filter cutoff frequencies canbe made adjustable by the digital controller. Also, the gain of theamplifiers can be made adjustable as in variable gain amplifier and caneither be controlled with a feedback loop. Additionally, the samplingfrequency and resolution can also be made controllable. One or more ofthe above described components of the AFE can also be deactivated andbypassed for power savings and versatility. For example, it may bedesirable to bypass the AC-coupling block and the low noise amplifierand simply low pass filter the signal and convert it to digitalrepresentation if the sensed signal has large amplitude and does notcontain large DC component.

The electrodes and electrode interface circuits can also sense actionpotentials, neural activity signals, muscular activity signals, andother biological, chemical, biochemical, or physiological signals. Forelectrical signals, electrodes act as transducers to supply signal tothe sensing interface. The sensing interface can comprise an optionalcoupling network, low noise amplifier, variable gain amplifier, tunablefilter, and ADC to digitize the signal and feed it to the controller.The above mentioned components make up an analog front end (AFE) for theelectrode interface. The AFE for communication can be reconfigured andreused for sensing physiological signals when not being used forcommunication. Alternatively, a dedicated AFE for physiological signalsensing can be used on the external device. The same electrodes can beused for communication or separate electrodes or electrode pairs can beused for communication and for physiological signal sensing.Additionally, these electrodes and electrode interface circuits can alsobe used to sense the actual delivered therapy parameters and adjust theparameters based on the measured values. Because in some cases theimplantable system and/or device(s) may not include a precise clockreference, it may be difficult to achieve precise timing. Therefore, itis very valuable to have the ability to sense the actual therapyparameters and compare them to desired parameters and then adjust theseparameters until actual therapy parameters match the desired parameters.The controller on the external device 2030 can be programmed to controlwhen sensing of these various parameters occurs. For example, duringtherapy delivery, therapy parameters can be sensed. When therapy is notbeing delivered and the implantable device 2010 is communicating withexternal device 2030, the controller can configure the AFE to sense thereverse link data. When neither is occurring, the controller canconfigure the AFE to sense physiological signals.

Matching gels, adhesive gels, conductive gels, short-wear gels,extended-wear gels, hydrogels, can be used to ensure good contactbetween the conduction electrodes and tissue. These gels can improvemismatch between impedances, improve conduction, and improve comfort forthe patient. They can also improve the safety characteristics of theoverall system by offering better heat management and/or impedancecontrol of the interface.

For both the forward and reverse communication systems, the datatransfer needs to safe, reliable, and private. The preferred ASK-PWmethod for forward data transfer may offer advantages in safety becauseit minimizes effects on power delivery, allowing for higher powertransfer efficiency and therefore less tissue heating due to the powercarrier. The interaction with the implantable device 2010 is alsoprotected in the sense that the signal may be sent on the power signal,which may be placed on the surface of the skin to send sufficient powerfor operation. This may ensure that interference from other types ofelectromagnetic radiation will not disturb the operation of the device.Additionally, the implantable device 2010 may only operate when verifieddata is received, ensuring that the device is inactive when not givenspecific instructions. The data sent from the implant can be keptprivate because sensing it requires an antenna in very close proximity,preventing other devices or antennas from detecting the signal. Thecommunication protocols can be unique to the device and can includeencryption to further ensure privacy.

In many embodiments, the transmitter transfers electromagnetic energy tothe implant at frequencies in the low-GHz range. This frequency rangehas advantages for very small antennas operating in tissue environments.The carrier frequency can be generated in a number of ways, includingoscillators or signal generators. This carrier may then be modulated byintroducing a controllable impedance in the RF path to introducemismatch and therefore controllably alter the amplitude of thetransmitted signal. This method can be implemented with transmissionlines and transistors. One implementation uses a BJT transistor tied tothe RF path with a transmission line to ground, and by controlling thevoltage at the base, a variable impedance can be introduced. This methodcan modulate the amplitude from 0-100%. Lower depths may have a minimaleffect on power transfer, however data is received more robustly withlarger modulation depths. The signal may be amplified after modulationand then transmitted through one or more antennas. This antenna may bematched to the frequency of the carrier to maximize the radiatedelectromagnetic energy. For implantable devices 2010 with backscatteringdata links, this antenna will be capable of sensing small amounts ofreflected energy and recovering the intended information. Alternatively,for implantable devices 2010 transferring data with small electricalsignals transferred through tissue, the external device can includeelectrical contacts with the surface of the skin to sense and recoverthese signals.

For both the forward and reverse communication links, the data transfercan be transferred digitally, and so any form of conventional errordetection and correction can be used. This can accomplished throughrepetition codes, parity bits, checksums, error correcting codes, or anymethod that is familiar to those skilled in the art. For the forwarddata link to the implant, the preferred embodiment includes an ID codeand a preamble that may be present before data capture starts. Once thedata capture phase completes, error detection and correction can beperformed for additional protection against errors. For the reverse datalink, there can be significantly more errors because of the difficultyof low-power communication through tissue environments. In these cases,error correction could be essential, and any of the previous correctionmethods can be used. The transmitter can also acknowledge the datathrough a handshake with the implant or request that data be resent iferrors occurred.

Multiple implantable and/or external devices may need to be deployed foreither monitoring physiological activity or delivering therapy atmultiple locations in parallel. Because there is a need to get data fromand send commands to all of these devices that are located roughly inthe same area, it may be necessary to use a multiple access scheme witha single external device. Time division multiple access (TDMA) basedscheme. as shown for example by the timing diagram 3500 of FIG. 35, canbe used to achieve communication with multiple devices. Each implantabledevice 2010 may have its own time slot to communicate to the externalreader. Each device can be assigned its own unique identification (ID).For example, FIG. 34 shows a method 3400 of assigning unique IDs to eachdevice which can be used in multiple access communication protocols. Theexternal reader may interrogate the individual implantable devices 2010in a sequential manner by transmitting data packets with an ID for whichthe data packet is intended. Once the implantable device 2010 receivesan ID that matches its own, it will act based on the data contained inthe packet and may transmit a reverse data packet to the external readerwith its own ID. This way only one implant communicates to the externalreader at a time, avoiding data collisions. The interrogation period forall devices is short enough compared to physiological activity toachieve high temporal resolution.

Another multiple access scheme which can be used for reverse datatransmission may be code division multiple access (CDMA). A group oforthogonal codes can be used to encode outgoing data packet prior totransmission. Since each device which is communicating back to theexternal reader would have a code which is orthogonal to that of otherdevices, data collision can be avoided even if multiple implantabledevices communicated with the external device in the same time frame.TDMA scheme can be used for forward data transmission and either CDMA orTDMA may be used for reverse data transmission.

CDMA for reverse data transmission from implants or implantable devicesto external device is also beneficial to provide feedback from multipleimplanted implantable devices while positioning the external device inthe optimal location. With only a single implanted implantable device,there is often no ambiguity which device is transmitting data to theexternal reader. Therefore, a simplified protocol can be used to deriveinformation about the wireless link quality while positioning theexternal device. However, when more than one implantable device isimplanted, either the protocol has to be more complex to accommodatemore implants without ambiguity or devices need to be able tocommunicate asynchronously and possibly concurrently. More complexwireless link quality feedback and positioning protocol unnecessarilycomplicates and makes the process of positioning the external devicelonger and less desirable for the user of such device(s). Therefore, apreferred embodiment uses CDMA scheme where devices can communicate tothe external device concurrently while the wireless link is beingestablished. This way, the external device(s) 2030 can receive data fromone or multiple implantable devices 2010 unambiguously and providefeedback and guidance to the user on what the optimal position of theexternal device(s) 2030 is.

In some embodiments, the protocol for positioning of the externaldevice(s) 2030 to achieve wireless link of acceptable quality isoutlined in the following. The external device(s) 2030 may transmit ahigher power level than usual during the positioning process in order toaccelerate and ease the positioning process. When an implantable device2010 is powered on, power-on-reset (POR) signal can be generated andcauses the implantable device controller to reset itself to a knownstate. This signal also triggers the controller to transmit a data frameto the external device 2030 to indicate that the controller has beenreset. This can notify the external device 2030 that the particularimplantable device 2010 which transmitted the data has receivedsufficient amount of power to turn on and reset itself. This limitedinformation may be insufficient to derive information about the wirelesslink quality, however. Therefore, additional information may benecessary. This additional information can be on the rate of charging ofan energy storage element on the implantable device, such as capacitoror battery. For example, the implantable device 2010 could transmit adata packet to the external device when its energy storage is charged toparticular percentages of the capacity in certain incremental steps,such as 0% to 100% in 10% increments. The external reader could theninterpret how much power is being delivered to the implant. If thestorage element gets fully charged, the external device 2030 cantransmit a command to discharge the element through a built-in shuntingnetwork on the implant, acting as an internal dummy load. Also, theoutput power level on the external device 2030 can be adjusted to speedup the search for optimal operation parameters, including externalantenna position. Therefore, this added information can be used by theexternal device to derive either relative or absolute information aboutthe wireless link quality and suggest an alternative antennaorientation, output power level, operating frequency, impedance matchingnetwork configuration in case it is tunable, and other parameters thataffect the wireless link quality.

In case of an implanted system having a single implantable device 2010,the antenna orientation can be adjusted based on a gradient searchalgorithm until a maximum in the wireless link quality is found based onthe feedback received from the implant, as described above. The outputpower level can then be adjusted based on the therapy parameters andcharge and discharge rates on the implant. The power level adjustmentscan be done when the patch is placed or periodically, to ensure that theimplant receives sufficient but not excessive amount of power, whichwould result in inefficient system operation. This can be accomplishedby monitoring charge/discharge rate while starting at a high outputpower level and slowly reducing the output power level until deliveredamount of power becomes insufficient for device operation, which wouldoccur when discharge rate is faster than charge rate.

In case of an implanted system having multiple implantable devices 2010,the antenna orientation can be adjusted based on feedback from multipleimplants until all implants receive sufficient amount of power. This canbe achieved by monitoring quality of individual wireless links betweenthe external device(s) and each implant. Once optimal position of theexternal antenna for every implant is known, a good position whichaccommodates all the implants in the best possible way can bedetermined. In case there may not be position which accommodates all theimplantable devices 2010, priority can be given to certain implants anda biased position which accommodates devices with higher priority can bedetermined. Algorithms that weigh importance of certain implants can beused and position can be determined based on these weights andpriorities. For example, if two implantable devices 2010 are deliveringenergy to tissue to achieve desired therapeutic effects, a doctor incharge of therapy or potentially even the overall system itself candetermine that one of the two implants has a stronger effect than theother and the external antenna position can be biased toward the moreimportant implant while sacrificing the wireless link quality of theless important implant. Overall, this may be more advantageous for theoperation of the overall system as a whole. Alternatively, implantabledevices 2010 with higher power consumption can be given a higherpriority than those with lower power consumption in order to achieve thehighest power efficiency of the overall system.

Multiple devices may have the same ID if similar or identicalfunctionality is required in the same time frame. In this case, theexternal system would act as a broadcasting station for multipleimplants or implantable devices. All implantable devices with thematching ID would act upon data which they receive in the forward datapacket, causing them to be synchronized to the same external system'sclock.

The ID programmability for each external device 2030 can be achieved viawirebonding, solder bumping or a technique which provides an inexpensiveyet effective way to reuse the same integrated circuit and same boardand simply modify the pattern in which ID pads are wirebonded—either toVDD or GND potential—thus assigning the ID to each device, as shown inFIG. 34. This method 3400 can also be used to program a particular codefor every implant if CDMA scheme is used for communications.Alternatively, an external device 2030 can have non-volatile memory orregisters which can be programmed, setting the device ID and code ifneeded.

A sample timing diagram illustrating TDMA operation is shown in FIG. 35.Forward data from the external reader to the implantable device 2010 isshown by arrows 3510, and reverse data from the implant to the externalreader is shown in by arrows 3520. From FIG. 35, it can be seen that theforward data packet comprises a prefix (preamble), implant ID, followedby data which includes encoding to handle errors and improve signalintegrity, such as run length limiting codes. Once the implantabledevice 2010 receives the matching ID and error-free data, the internalclock is enabled and, after some delay, the data is transmitted backfrom the device to the external reader. The delay may be necessary toensure that the forward data link does not interfere with the on-chipanalog sensing interface which can be sensitive to power supplyfluctuations caused by RF amplitude fluctuations. Also, the delay canhelp demodulate the reverse data packet at the external reader whenbackscatter or load modulation is used. The reverse data packet containsa preamble, ID, and data which include encoding to handle errors andimprove signal integrity. The entire forward and reverse datatransaction could take on the order of 50 μsec or more due to highforward and reverse data rates, such as 0.1 μsec to 100 μsec. In somecases including the use of larger packet sizes, the transaction couldtake more than 100 μsec, such as 100 μsec-5 ms, or 500 μsec-1 ms. Incase the implantable device 2010 has a large number of registers whichneed to be programmed for proper implant operation, the implant can beprogrammed not within one but within multiple forward data packets. Inthat case, the forward data packet may contain address and value of theregister which needs to be programmed instead of programming allregisters at once. It could also take significantly less time than 50μsec if data rate is increased or if programming is performed withmultiple packets.

Feedback data from the implantable device 2010 can be used to adjust theexternal device 2030 power levels in order to provide sufficient powerto one or more implantable devices 2010 while not exceeding thenecessary amount of power. This may be beneficial in order to savebattery life on the external device 2030. Implantable devices 2010 canprovide information to the external device(s) or patch(es) to controlthe output power level in a closed-loop configuration. This feedbackinformation can be provided periodically, upon request, or continuouslydepending on the specific use case. The power levels may also need to beadjusted during varying patient physical activity, changingenvironmental conditions, and other situations that may perturb the linkgain between implants and the external patch. The feedback data caninclude charge and discharge rates of the implants, as described inalgorithm for antenna positioning section of this document. The powerlevels can further be adjusted during data transmission and/or receptionphases in order to improve data link quality. The power levels can alsobe adjusted periodically to improve link gain. For example, bursts ofhigh power transmissions can be used to quickly charge the implants ifneeded.

The matching network, operating frequency, and other link gain and datalink parameters can be adjusted to accommodate varying environmentconditions and unpredictable environments. The matching network canutilize an array of components that can be configured using a searchingalgorithm to select the optimal component or combination of componentsbased on the desired search criterion, such as the maximum link gain orthe maximum data rate. Furthermore, the carrier frequency can also beadjusted to select optimum frequency of operation. Two or moreparameters can be swept in a nested loop or using a more sophisticatedalgorithm, such as a gradient search or MSE algorithm to determineoptimal parameters for operation. The frequency of operation may be auseful parameter for maximizing link gain, especially in situations whenone or more implants do not include an adjustable or tunable matchingnetwork. In those cases, the external transmitter can sweep thefrequency of operation while adjusting matching network to maintain goodmatch between antenna and transmitting circuits in order to improvepower transfer characteristics to the implant. The maximum link gainfrequency can then be identified and selected based on the algorithmsdescribed earlier, which may require feedback information from theimplant. Frequency selection can compensate for unpredictable operatingenvironments or changes in environment, and it can be readjusted ifthese types of changes reduce performance. The power transmitted canthen be adjusted based on the therapy and the link performance to ensurea sufficient amount of power is delivered to one or more implants andthat only insignificant amount of power is wasted by minimizing excessoutput power. Some matching network and link gain optimizationtechniques are described in U.S. patent application Ser. No. 12/485,641by Stephen O'Driscoll, et al. Moreover, the described configurationoptimization can be carried out periodically, only once afterimplantation, on demand, or continuously. It can also be done in aclosed-loop manner with or without the patient's knowledge, in order toimprove therapy adherence. Multiple carrier frequencies can be utilizedby the external device to improve link gain with one or more implants.This may be especially beneficial in the case of multiple implants withnon-tunable matching networks and unpredictable or varying environments.In those cases, the external transmitter can transmit several carriersat different frequencies to accommodate each individual implant'sfrequency of operation. The external transmitter can utilize multipletuned antennas, or broadband antenna(s). Alternatively, a single antennawith tunable matching network could be used with time-domain multipleaccess approach. Other similar techniques could be utilized toaccommodate multiple carriers.

Similar to optimizing power link gain, the data link gain can also beoptimized. This optimization can be based on minimizing bit error rate,such as by utilizing a PRBS data and counting errors and adjusting datalink parameters based on this feedback. The adjustable data linkparameters are described in this document and are also described in U.S.patent application Ser. Nos. 13/734,772 and 14/043,023.

Mismatch in impedances can be sensed using multiple methods, as wasdescribed earlier, such as by sensing the reflection coefficient orstanding wave ratio by relying on a directional coupler or circulator,or other methods, such as by sensing temperature of the transmittingcircuits and/or antenna. Other methods for sensing and adjustingmatching network can be found in U.S. patent application Ser. Nos.12/485,641 and 14/043,023. These methods can also be used to detectfailures in the overall system. Once mismatch or temperature exceeds apredetermined threshold, the overall system can classify the event orcondition as failure and take appropriate actions in accordance withfailure handling algorithms, including disabling the overall system andnotifying the users.

The external devices 2030 can also be configured to monitor the activityof the therapy, power link, data link, sensing circuitry, antenna,impedances, and other measurable parameters of the overall system inorder to prevent malfunction, failures, or unintended operation. Variousfailure detection mechanisms can be implemented in the overall system.The power link can be monitored via temperature of the overall system,reflection coefficient to monitor impedance mismatch, electric currentdraw, and other parameters which would change from baseline during afailure. Bit error rate monitors can be utilized to estimate data linkquality. For instance, in the event of an antenna failure, the impedancewould be become mismatched, causing a significant reflection of energy.This in turn would cause the reflection coefficient to become high, andcould increase the external device temperature. The fault in the overallsystem operation could be detected by monitoring temperature, reflectioncoefficient, standing wave ratios, or combinations thereof and theon-system controller could respond to such an event in accordance to apre-programmed safety protocol. Additionally, in the case of a severe ordangerous failure, an automatic kill-switch could be triggered. Onepossible action for this failure event could be to shut down the overallsystem and notify the user of the failure and its specifics. In caseswhen failures could be catastrophic, emergency personnel, the patient'scaregiver and/or doctor could be alerted of this event, as well. Otherfailure detection mechanisms could involve estimating the quality of thepower link and/or data link, a comparison of therapeutic parameters withdesired parameters, interference detection from other devices in similaroperating frequency band, and/or harsh environments which are adverse todevice operation, such as radiation or presence of strong electric ormagnetic fields. Appropriate failure handling protocols would cause theoverall system to respond to these various conditions in a way tominimize any harm to the patient, the overall system, and surroundingenvironment. Calibration and/or system adjustments can be done based onthe failure monitors. Some of the possible failures also includeinadequate or nonexistent power and/or data link or lack of expectedresponse from one or more implantable devices. Other failure mechanismsinvolve imbalance of delivered charge, failures in hermetic packagingwhich would cause shift in frequency and changes in performance,impedance changes in leads and tissue-electrode interface, impedancechanges in antenna, and other parameters.

Implantable devices 2010 can also have built-in kill-switch or temporarydisable switch in order to permanently or temporarily disable device.Disabling of the implantable device 2010 can be done by shorting powerand ground terminals of the implant, shorting antenna terminals, and/orshorting all electrodes together. This would prevent the device fromharvesting energy and from delivering stimulation energy to tissue. Thekill-switch could be activated remotely via magnetic field, such as in areed switch or relay. Other options could be through fuse, non-volatilememory, mechanical options, physical shorting such as shorting certainterminals.

A linear xy stage can be used by a patient, a doctor, or even beincorporated into the external system in order to automate positioning.The positioning can be done every time when the external system is beingpositioned, or can even be readjusted periodically. Alternatively, thepositioning can be optimized with a specially designed xy stage or asimilar positioner and the optimal location of the implant can be markedon the skin of the patient for ease and repeatability of subsequentpositioning. Readjustment can be done periodically but with lowfrequency to ensure that the marked position is still optimal and tocompensate for any changes in the operating environment which may affectthe optimal position of the antenna 2210 on the external devices=2030.

The external device 2030 may be operated by either a doctor or patientdepending on the intended use of the external device 2030 and theoverall system 2000. This external device 2030 can be powered bybatteries or be plugged in to a wall depending on where and howtreatment is delivered. The external patch can have built-in orreplaceable batteries that can be easily swapped by a patient, as shownin FIG. 25. The batteries can be primary cell or rechargeable. In casethere are multiple external patches on a patient, they can be powered bya single battery pack to which they are tethered; or each patch cancontain its own battery in order to avoid wired tethering. These setupsare depicted in FIGS. 23a -23 d, which also shows networkconfigurations. In case networking or therapeutic coordination isnecessary between external patches, they can communicate using wirelesscommunication methods or wired communication methods if they aretethered. Each external patch may have multiple devices within itsnetwork to coordinate therapies and/or diagnoses. The external devicesor patches 2030, furthermore, can be a part of a larger network which isconnected to a handheld device and/or another main controller device.This makes up a super-network of coordinated implants which are all partof this network via the external devices or patches 2030. This networkcan achieve improved therapeutic outcomes with the use of localizedand/or distributed diagnostics and/or therapeutics. The synchronizationcan be done at any level of the network—at implant level, external patchlevel, or the super node level (handheld controller or other similardevice). FIG. 27 shows a possible configuration 2700 of a readerinterfacing with multiple devices, and FIG. 28 depicts a configurableinterface 2800 that can operate with a variety of sensors, actuators, orother elements. Additionally, other coordination operations can be doneon all devices in the network, such as the calibration of devices,therapeutic parameters, sensing parameters, adjustments to environmentalconditions, and others. The environmental condition changes may include:changes in patient physical activity; patient stress levels; externalenvironment adjustments to compensate for temperature, humidity, andothers; presence of potentially harmful conditions to devices in thenetwork caused by extraneous electric or magnetic fields, such as duringMRI, cat-scan, X-Ray, ultrasound, or potentially due to use ofdefibrillators, or interference from other devices. In those cases,depending on the level of severity of the environmental conditions, theoperation and/or therapy can be adjusted to compensate for the changes,or in some cases, the devices can be instructed to be turned off inorder to prevent any malfunction, damage, or failure. The networkdevices may also communicate with computers and/or smart phones to relayinformation about the operation of the overall system and to allow forreconfiguration of the overall system. In order to communicate withexternal devices 2030 other than implantable devices 2010, the externaldevice(s) or patch(es) can have additional communication interfaces.These interfaces connect the external device(s) 2030 to the outside andprovide an ability to interface with users to program the externaldevice(s) 2030, reconfigure the device(s) in part or in its entirety,program or reconfigure each individual implant of the implantabledevice(s) 2010 or the external device 2030, monitor the external device2030 and its functionality and status, monitor individual implantfunctionality and status, monitor status of the therapy or diagnosticresults, securely transfer and save data. This communication with theexternal infrastructure, such as personal computer, smart phone, orcloud computing, can be accomplished utilizing any existing wirelessprotocols, such as Bluetooth, ZigBee, WiFi, Qualcomm 2net, MICS, ISM,WMTS, MedRadio, MNN, MBAN, cellular communications, RFID or existingwired protocols, such as USB or ThunderBolt which could also be used tocharge the external device(s). Collectively, this interface of theexternal devices 2030 to things outside of human body is referred to asexternal interface.

The rechargeable battery 2510 can be recharged using tethered methods,such as by plugging into a charger, or wirelessly. The battery 2510 canbe recharged wirelessly using inductive coupling, mid-field powering, orfar-field beam steering approaches. In case of near-field or mid-fieldpowering, the transmitting antenna can be aligned with the externalpatch receiving antenna using passive or active alignment methods. Someexamples of passive alignment methods include: mating mechanicalprotrusions which can lock the two antennas in fixed position forrecharging; permanent magnets in the recharger and the external deviceor patch 2030, such that the magnets align the two antennas; and othersimilar methods. The active alignment methods may include: usingpermanent magnet and an electromagnet to align the antennas; sensingcoupling between two antennas and providing feedback to one of theantennas to reposition it with respect to the fixed antenna; and othersimilar methods. FIG. 24 depicts a magnetic alignment sub-system forwireless recharging of the external system or device(s).

Referring to FIG. 24, the external device 2030 may be wirelesslyrecharged. Power may be supplied with an external power supply 2410which may power an external charging member 2420 which may comprise amagnet or mating mechanical protrusion 2430 for external coil alignmentwith a complementary magnet or mechanical protrusion for external coilalignment 2435 of the external device 2030. When the external chargingmember 2420 and the external device 2030 are aligned, the inductivecoils 2440 of the external charging member 2420 may be aligned with theinductive coils 2445 of the external charging member 2420 so that theexternal device 2030 may be charged.

The external interface may use secure communications in order to preventany non-secure access to information from unauthorized users or devices.Additionally, authorization can be required to change therapy parameterswhich would affect the course of treatment. Different authorizationtiers can be implemented that enable various levels of access to theprogrammability and data of the overall system. For example, doctorauthorization level provides an ability to change therapeutic parametersof the overall system, and provides access to collected data abouttherapy status and history as well as any relevant information aboutcollected physiological data. Patient authorization level can provideinformation about the status of the overall system, such as batterylevel on the external device(s) as well as some additional informationwhich can be useful for the patient. A patient may also be able to makesome minor adjustments to the operation of the overall system which liewithin certain boundaries pre-set by a doctor who would not dramaticallyalter the course of treatment or compromise safety of the patient.

The external device 2030 can also send reminders, alerts, and othertypes of notifications to authorized people through the externalinterface. For example, if a patient does not put on the external device2030 during the programmed therapy window, the overall system may notifythe patient and/or the patient's doctor that the therapy is not beingfollowed. These notifications and reminders can improve patientcompliance and can also serve as a feedback for a doctor about thetherapy effectiveness.

The external device 2030 may also offload some of the processing andstorage needs to the external computing infrastructure by transferringraw or partially processed data that it collects through the externalinterface. The infrastructure can then notify the external device(s) ifany action is required, such as change in therapeutic parameters.Notification may also be post-processed data which is formulated foreasier visualization by a patient or doctor. For example, in case ofseizure prevention the implant can collect raw data and rely on theexternal device or infrastructure to predict the onset of seizures andthen notify the external device that it needs to administer a treatmentor stimulate certain parts of brain in order to prevent the seizure.

The handheld device 2020 can contain user interfaces for input andoutput, such as touch screen display, an LCD or other conventionaldisplay, speaker, vibration element, light emitting element, and othersfor output, and keyboards, buttons, touch screen interface, switches,and other similar input interfaces to program, monitor, and control thetherapy and/or diagnostic devices within the network. Multiple externalpatches can be controlled from the same handheld device. In turn, thehandheld device can have access to and control of each individualimplantable device via one or more external patches, as describedearlier.

Although other components which are essential or optional to theoperation of the integrated circuit have not been described explicitlyare included implicitly. Such components may include power-on-resetcircuit (POR), calibration circuits, memory, timing and delay circuits,and other circuits not explicitly stated in this invention. Theirimplementation, functionality, and how they fit into the overall systemis obvious to those skilled in the art of integrated circuit design canbe accomplished with a variety of methods that relate to the overallsystem architecture.

The one or more external devices and the one or more implantable devices2010 can work individually or coordinate in a network to treat a varietyof conditions. The one or more implantable devices 2010 can be places inone or more of the following sites for sensing and/or treatment: thetibial nerve (and/or sensory fibers that lead to the tibial nerve); theoccipital nerve; the sphenopalatine ganglion; the sacral and/or pudendalnerve; target sites in the brain, such as the thalamus; the vagus nerve;baroreceptors in a blood vessel wall, such as in the carotid artery;along, in, or proximal to the spinal cord; one or more muscles; themedial nerve; the hypoglossal nerve and/or one or more muscles of thetongue; cardiac tissue; the anal sphincter; peripheral nerves of thespinal cord, including locations around the back; the dorsal rootganglion; and motor nerves and/or muscles. The system or apparatus canbe used to treat one or more of the following: migraine; clusterheadaches; urge incontinence; tremor; obsessive compulsive disorder;depression; epilepsy; inflammation; tinnitus; high blood pressure; pain;muscle pain; carpal tunnel syndrome; obstructive sleep apnea; pace ordefibrillate the heart; dystonia; interstitial cystitis; gastroparesis;obesity; fecal incontinence; bowel disorders; chronic pain; improvingmobility.

These system or apparatuses of the present disclosure can be effectivefor both chronic and acute treatments, and can withstand long-termimplantation and use under various environments. These systems orapparatuses can include devices that produce custom waveforms forstimulation that can be tailored to the treatment and to the specificpatient. These systems or apparatuses can incorporate two-way high-speedcommunication with an external device. These systems or apparatuses(e.g. implantable devices) use novel methods of energy delivery, energymanagement, communications, activation and suppression of physiologicalactivity as will be described herein. These implantable devices andexternal devices also have novel form factors and encapsulation,allowing for flexible treatments, simple implantation, and reliablelong-term use. There is also a discussion of applications of thesemethods, systems, and apparatus and potential variations to accommodatedifferent uses, including both therapies and trialing.

Implantable devices have a limited power budget, which restricts bothminiaturization and functionality. Neuromodulation devices can requiresignificant power to provide therapy because of the relatively highvoltage and current requirements needed to drive stimulation. For fullywireless devices, the power limitation is typically the designconstraint and limits the performance of the device. An overall system410 of the present inventive concepts is shown in FIG. 36, and isdescribed in more detail in the references incorporated herein. FIG. 36shows the minimally invasive implantable device 4110 that is controlledand powered from a device external to the body. A basic block diagram ofthe external device 100 is shown in FIG. 37 and a basic block diagram ofthe implantable device 4110 is shown in FIG. 38. The external device4100 can have all its elements integrated into a single component, or itcan be divided into several discrete components that are tethered oruntethered. Additionally, the overall system 411 can operate withmultiple copies of the external devices and/or the internal devices(e.g. multiple discrete external components and/or multiple discreteimplantable components) to form a network or system of external andinternal devices, respectively. The elements of the system 411 can allowminiaturization to mm and sub-mm sizes while offering the flexibility tooperate with different power budgets and offer different features andform factors. These advantages may be partly accomplished by the abilityof the implantable device 4110 to interface with different antennas andan on-board intelligent power management sub-system as described aboveand herein. The implantable device 4110 can include a controller thatconfigures the on-board circuitry, a pulse generator that can producecustom stimulation waveforms to accommodate the intended treatment, andone or more antennas. This pulse generator could control amplitude,timing and frequency, pulse duration, duty cycle, and/or polarity. Thesmall size of the implant 4110 can allow for a minimally invasiveimplantation process such as with a needle injection system, anendoscope, or a laparoscopic technique as will be described further. Theexternal device 4100 may include one or more transmission antennas thatmay be placed near the surface of the skin in close proximity to theantenna of the implant 4110, which may be implanted inside the body.This external device 4100 can transfer both power and data to theimplantable device 4110, and operates with either batteries or with awall outlet. The external device 4100 may have a separate communicationprotocol, such as Bluetooth, for interfacing with computers, smartphones, a handheld device; the Internet; a local area network (LAN);and/or other devices. Data is transferred at speeds up to and exceeding20 Mbps to accommodate configuration and control of the one or moreimplantable devices as well as real-time treatment adjustments. Dataand/or power can also be transferred to multiple devices (e.g. multiplediscrete implantable devices) simultaneously (e.g., power is transferredsimultaneously and communications with multiple implantable devices canbe done in discrete time slots, as in case of time domain multipleaccess) and the high-speed of communication allows for severalimplantable devices to adapt and adjust in real-time. Sensors can beincorporated with the implantable devices and/or external devices andalso make use of the high-speed communication for diagnostics orreal-time feedback of physiological parameters to inform the doctor orpatient of the functionality of overall system 411 (or a component ofoverall system 411) or to provide patient physiologic informationfeedback to the overall system 411 to adapt the treatment.

The implantable device 4110 is controlled by an external device 4100that can be designed to accommodate the particular application and itsintended use. This external device 4100 can include one or more antennas4150 for transmitting and receiving RF signals, a controller 4140 forcontrolling the communications or other operations of the overall system(e.g. therapeutic parameters, neuromodulation parameters, closed-loopadaptation of therapy based on feedback from sensors), and a powersource 4130, such as a battery. These external device 4100 elements canbe combined into a single discrete component or divided into severalcomponents. In some embodiments, a power source 4130 (e.g. battery) andcontroller are surrounded by a single enclosure, and one or moreantennas 4150 are tethered to this enclosure via a wire (e.g. cable orinterconnect 4310), as depicted in FIG. 39 and FIG. 40. There, a userinterface and/or display may be implemented (e.g. on the enclosuresurrounding the power source and controller), allowing the user to view,interact, and/or adapt the operation of the overall system 411. The userinterface could comprise button(s), a touchscreen display, knob(s),keyboard, keypad, display, microphone, light, speaker and/or othercomponents configured for user input and/or user output. Depending onthe intended use and application of the overall system 411, this userinteraction with the system or apparatus can have varying levels ofcomplexity. In these embodiments, one or more antennas 4150 could beattached to the skin directly through an adhesive or attached in closeproximity to skin with a belt, band, strap or other attachment element.An enclosure containing power supply 4130 and controller 4140 could betethered to this antenna and placed in a more comfortable or otherwiseconvenient location, such as in a pocket or clipped to a belt. Theantenna, adhesives, or other attachment elements can be designed to bedisposable after several days, weeks, or months of operation.Alternatively, the antenna, adhesives or other attachment elements, orother component of the external device, can be more permanent, lastingyears or longer. A battery (or a battery pack) can be charged while inthe enclosure, it could be removable from the enclosure to be chargedseparately, or it could be removable primary cell battery so it can bereplaced with another primary cell battery. These battery configurationswould allow the user to have multiple batteries for the one externaldevice and charge one battery while the other is in use with theexternal device.

In some embodiments of the external device 4100, a single enclosuresurrounds a power supply (e.g. battery) 4130, a controller 4140, and oneor more antennas 4150. In these embodiments, the enclosure could beattached directly to the skin through an adhesive or attached in closeproximity to the surface of the skin through a belt, band, strap, orother attachment element. An example of these embodiments is depicted inFIG. 41. The user interface could be implemented on the enclosure,allowing the user to view, interact, and/or adapt the operation of theoverall system 411. The user interface could comprise button(s), atouchscreen display, knob(s), keyboard, keypad, display, microphone,light, speaker and/or other component configured for user input and/oruser output. Depending on the intended use and application, thisinteraction can have varying levels of complexity. The adhesives orother attachment elements can be separate from the enclosure and can bedesigned to be disposable after several days, weeks, or months ofoperation. Alternatively, the adhesives or other attachment elements canbe more permanent, lasting years or more. A battery can be charged whilein the enclosure, or it could be removable from the enclosure to becharged separately. These battery configurations would allow the user tohave multiple batteries for the external device and charge one batterywhile the other is in use with the external device.

In some embodiments of the external device 4100, a power supply (e.g.battery) 4130 and controller 4140 are surrounded by one enclosure, andone or more antennas 4150, each attached to a relay or communicationelectronics 4160, have the ability to wirelessly communicate with thecontroller, such as is depicted in FIG. 42. This wireless communicationcan be accomplished with Bluetooth, WiFi, ZigBee, Qualcomm 2net, MICS,ISM, WMTS, MedRadio, MNN, MBAN, cellular communications, and/or RFIDcommunications. This arrangement can also be used to configure a networkwith multiple external devices, and this is depicted in FIG. 43 a. Inthese embodiments, the user interface could be implemented on theenclosure with the power source 4130 and controller 4140 that canwirelessly communicate with the antenna, allowing the user to view,interact, and/or adapt the operation of the overall system. The antennacan have its own power source (e.g. replaceable, swappable, orpermanent, as described hereinabove) and communication electronics 4160.The user interface could comprise buttons, a touchscreen display,knob(s), keyboard, keypad, display, microphone, light, speaker and/orother component configured for user input and/or user output. Dependingon the intended use and application, this interaction can have varyinglevels of complexity. With these embodiments, the antenna could beattached to the skin directly through an adhesive or attached in closeproximity to skin with a belt, band, strap or other attachment element.The enclosure containing a power source 4130 and controller 4140 couldbe placed in a more comfortable or otherwise convenient location withinthe range of the wireless communications to this antenna, such as in apocket or clipped to a belt. The antenna, adhesives, or other attachmentelements can be designed to be disposable after several days, weeks, ormonths of operation. Alternatively, the antenna, adhesives, and/or otherattachment elements can be more permanent, lasting years or longer.Batteries can be charged while in their respective enclosures, or theycan be removable from their respective enclosures to be chargedseparately. These battery configurations would allow the user to havemultiple batteries for the external device and charge the extrabatteries while the external device is in use.

In some embodiments of the external device 4100, a power supply 4130(e.g. a battery), a controller 4140, and one or more antennas 4150 areall integrated into an attachment assembly 4170 that may include a belt,band, strap, and/or other article of clothing. In this embodiment, theantenna would be attached in close proximity to the surface of the skinat a designated location on the attachment assembly 4170. Thisembodiment is depicted in FIG. 44. The user interface can be positionedin a convenient location on the attachment assembly 4170, allowing theuser to view, interact, and/or adapt the operation of the overall system411. Alternatively or additionally, the user interface can be untetheredhandheld device 4120 for improved convenience of controlling the overallsystem 411, wirelessly coupled to communicate with the rest of theexternal system. The user interface could consist of button(s), atouchscreen display, knob(s), keyboard, keypad, display, microphone,light, speaker and/or other component configured for user input and/oruser output. Depending on the intended use and application, thisinteraction can have varying levels of complexity. Elements of theattachment assembly 4170 can be designed to be disposable after days,weeks, or months of operation. A battery can be charged while in theexternal device(s), or it could be removable from the external device(s)to be charged separately. These battery configurations would allow theuser to have multiple batteries for the external device(s) and chargeone battery while the other is in use with the external device(s).

In some embodiments of the external device 4100, a power supply 4130(e.g. a battery) and a controller 4140 are integrated into an attachmentassembly 4170 that can include a belt, band, strap, or other article ofclothing, and one or more antennas 4150 are separately placed in thedesired position on the body with an adhesive or other attachmentelement. The one or more antennas 4150 can be tethered with a wire oruntethered and communicate with the controller 4140 through a wirelesscommunication method. This embodiment is depicted in FIG. 45. Thissystem may allow the patient to comfortably adjust the bulk of thecomponents without affecting the antenna placement. The user interfacecould be implemented in a convenient location on an enclosure of theexternal device 4100 or through a separate wireless controller, allowingthe user to view, interact, and/or adapt the operation of the overallsystem 411. The user interface could comprise buttons, a touchscreendisplay, knob(s), keyboard, keypad, display, microphone, light, speakerand/or other component configured for user input and/or user output.Depending on the intended use and application, this interaction can havevarying levels of complexity. Elements of the attachment assembly 4170and/or antenna 4150 can be designed to be disposable after days, weeks,or months of operation. The battery can be charged while in the externaldevice(s), or it could be removable from the external device(s) to becharged separately. These battery configurations would allow the user tohave multiple batteries for the external device(s) and charge onebattery while the other is in use with the external device(s).

In some embodiments of the external device 4100, a power supply 4130(e.g. a battery) and a controller 4140 are integrated into an attachmentassembly 4170 that can include a belt, band, strap, or other article ofclothing, and antennas 4150 are interspersed around this attachmentassembly 170 to maximize the coverage area of the transmitted signals.This embodiment is depicted in FIG. 46. This configuration would allowthe patient to comfortably adjust the bulk of the components whilemaintaining an effective wireless link with the implantable device 4110.Additionally, this external device 4100 can operate with multipleimplantable devices 4110 in different locations. The one or moredistributed antennas 4150 can all be activated or a subgroup comprisingone or more antennas 4150 can be selectively activated to optimizewireless link gain efficiency while saving power consumption. Thisoptimization can be performed based on feedback from one or moreimplantable devices 4110. Such link gain feedback and adjustmentalgorithm is described in more detail in provisional patent applicationNo. 62/053,085 titled “Method and Apparatus for Operation with MinimallyInvasive Neuromodulators,” filed on Sep. 19, 2014. The user interfacecould be implemented in a convenient location on the external device4100 or through a separate wireless device, allowing the user to view,interact, and/or adapt the operation of the overall system 411. The userinterface could comprise buttons, a touchscreen display, knob(s),keyboard, keypad, display, microphone, light, speaker and/or othercomponent configured for user input and/or user output. Depending on theintended use and application, this interaction can have varying levelsof complexity. Elements of the attachment assembly 4170 and/or antennacan be designed to be disposable after days, weeks, or months ofoperation. A battery can be charged while in the external device(s), orit could be removable from the external device(s) to be chargedseparately. These battery configurations may allow the user to havemultiple batteries for the external device(s) and charge one batterywhile the other is in use with the external device(s). As an additionalvariation to this embodiment, multiple power supplies 4130 (e.g.multiple batteries) could also be distributed along the attachmentassembly 4170 (i.e. positioned at different locations of the attachmentassembly), allowing additional power to be stored with a morecomfortable or otherwise convenient configuration. With distributedbatteries, the thickness of the attachment assembly 4170 could be moreuniform and the weight distribution along the attachment assembly 4170could be more balanced.

In some embodiments of the external device 4100, one or more antennas4150 can be constructed on a flexible substrate that conforms to thesurface of the skin and/or one or more antennas 4150 can be printed onthe skin directly using epidermal electronics. These antennaconfigurations offer additional convenience to the patient withoutsacrificing performance. One or more antennas 4150 comprising printedepidermal electronics can be electrically connected to a separateenclosure including a power supply 4130 (e.g. a battery) and acontroller 4140. Alternatively or additionally, one or more antennas4150 comprising printed epidermal electronics can wirelessly communicatewith a controller 4140, such as is described hereabove. Theseskin-attached and/or skin-printed antennas may need to be reapplied orreplaced periodically, which could be accomplished by either the doctoror the patient.

In some embodiments of the external device, multiple antennas can beused in the place of a single antenna. These antennas could either betethered or untethered (e.g. tethered or untethered to a controller 4140and/or external power source 4130). While a single antenna of theexternal device 4100 can power multiple implants in its relatively closeproximity, multiple antennas can be configured to allow implants atdifferent sites to be operated from a single external device 4100. Theseexternal device antennas can operate in coordination (e.g. transmitpower and/or communication simultaneously to implants), can operate ascommunication relays (e.g. relay received commands from the controllerto one or more implantable devices and from one or more implantabledevices to the controller while powering one or more implantable devicesdue to relay's proximity to one or more implantable devices), and canfunction as part of a network. Examples of this network are shown inFIG. 43.

In some embodiments of the external device 4100, the entire externaldevice 4100 can be designed to be disposable and replaced over thecourse of days, weeks, months, or years. This disposable device approachcan offer additional convenience to the patient by minimizing therequired maintenance for the duration of use. Alternatively, one or moreportions of the external device 4100 can be disposable while one or moreother portions are reusable. If the antenna 4150 is separate from thecontroller (either tethered or untethered), it could be designed in adisposable package that simplifies its use for the patient whilemaintaining high performance for the duration of use, such as when apower supply such as a rechargeable battery and/or the controller arereusable.

In some embodiments of the external device, the antenna can includeelements for tuning its position, orientation, and/or operatingenvironment to achieve better performance. This tuning can occur atlarge or small scales, and the adjustments can be automated or performedmanually. Information about communication and/or power links, overallsystem 411 performance, and/or overall system 411 characteristics can beprovided to assist this tuning for either the automatic or manualmethod.

The implantable device 4110 can also comprise several form factorsdepending on the intended use and the needs of the indication. In someembodiments, the implantable device 4110 comprises: one or more housings4200, one or more antennas 4240, one or more electrodes 4230, energyharvesting circuit, energy management circuit, one or more energystorage elements, a pulse generator, a controller, stimulation currentdriver, one or more sensors, communications circuits for receiving andsending data, calibration circuits, startup and power-on-reset circuits,memory circuits, timing circuits, and other auxiliary circuits, such asa matching network, that are necessary for proper implantable deviceoperation and a particular application (collectively electronics orcircuits 4241); and combinations of these. Different patients and/ortherapies may require different implantation sites, different electrodeplacement and/or configurations, different stimulation waveforms, and/ordifferent numbers of stimulation channels (e.g. each includingindependent energy delivery circuitry for one or more electrodes). Oneembodiment of the implantable device 4110 incorporates circuits 4241,antenna(s) 4240 and/or other elements into an implantable lead 4220,which includes one or more electrodes 4230 for interfacing with tissue.An example of this embodiment is shown in FIG. 51. The electronicsand/or antenna in the lead can be sealed (e.g. hermetically or otherwisesealed to prevent contamination from passing into and/or out of anenclosure), for long-term implanted use. In this embodiment, an antenna4240 can be distributed along the length of the lead to increase itsradar cross-section and/or alter its inductance (which alters theresonance). The length of a dipole antenna or the long dimension of aloop antenna could be changed by several centimeters, which increasesreceived power in proportion to the change in length and inductanceincreases in approximate proportion to the length as well. The lead 4220itself could include a variable number of connections depending on thetreatment (e.g. the number of stimulation channels that are necessary).In some embodiments, the implantable device can support 2, 4, 8, 16, 32,or more channels as any treatment can require (e.g. between one and 64electrodes). Additionally, the entire lead can be designed to beMRI-compatible by minimizing or eliminating induced currents and/or theuse of magnetic materials or ferromagnetic materials. In someembodiments of MRI-compatible leads 4220, the lead 4220 can haveconductive shield throughout the lead. In other embodiments, the lead4220 can have heat spreading elements built into the lead 4220. In yetother embodiments, reed switches or other relays or switches can be usedto disconnect electrodes 4230 from the interconnect 4310, to minimize orprevent MRI-induced current from flowing through tissue. The reed switchor other relays can be remotely activated prior to MRI use or by MRIfields and can be de-activated to return the implantable device tonormal operating condition after MRI use.

In some embodiments of the implantable device 4110, one or morefunctional elements (e.g. electronic components) are enclosed in ahousing 4200 (e.g. a sealed housing) on one end of a lead 4220. Thishousing can have a variety of shapes including cylindrical, rectangular,elliptical, spherical, or an irregular shape adapted to the specificrequirements of the overall system 411 and/or treatment. Embodiments ofthis housing are shown in FIG. 48, FIG. 49, FIG. 50, FIG. 51, and FIG.52. This housing 4200 can be sealed (e.g. hermetically sealed) ifdesirable with feedthroughs 4201 and/or wired or wireless connectorinterface 4210 for AC coupled channels (such as RF inputs for theantenna), stimulation channels, and/or sensors. The electrode 4230 canhave a variable number of connections depending on the treatment and thenumber of stimulation channels that are necessary. The device 4110 cansupport 4, 8, 16, 32, or more channels as any treatment can require(e.g., between one and 64 channels). Additionally, the entireimplantable device 4110 including the housing 4200 and the lead 4220 canbe designed to be MRI-compatible by minimizing or eliminating inducedcurrents and/or the use of magnetic materials or ferromagnetic materialsand as described hereinabove.

In some embodiments of the implantable device 4110, a lead 4220 isintegrated into the implantable device 4110 and/or is attached to theimplantable device 4110. This lead 4220, with or without an additionalhousing 4200, can be constructed to include a lumen 4260 to aid with theimplantation procedure. A stylet 4250, guide wire and/or otherinsertable filament (hereinafter “stylet”) can be used with this lumen4260 during the implantation procedure. These stylets 4250 can havebends or curves to assist with the guidance process, and in particularthe tip portion (i.e. distal portion) of the stylet 4250 can be straightor curved with a variable stiffness. This stylet configuration allowsthe lead 4220 to have a more controllable stiffness and therefore allowsthe implantation to more precisely controlled and guided. After the lead4220 is positioned in the desired location, the stylet 4250 can beremoved. For additional convenience, the stylet 4250 can be prepackagedinside the lumen 4260 of the lead 4220 and/or implantable device 4110,which will save time in the overall procedure.

In some embodiments of the implantable device 4110, the stiffness and/orshape of one or more portions of the implantable device 4110 can haveadditional control during implantation. This stiffness and/or shapecontrol can be accomplished through the use of shape-memory alloys,which can be reshaped with changes in temperature (or other controlparameter, such as applied current or voltage). These and other shapeand/or stiffness controllable materials allow for simplified and/orimproved manipulation and placement during implantation andpost-implantation of one or more portions the implantable device 4110.The implantable device 4110 (or a portion thereof) could be implanted ina configuration that simplifies the procedure, and then reshaped into anew configuration post-implantation. Alternatively, one or more portionsof the implantable device could be surrounded by a sheath 4270 of adesired stiffness during implantation, and the sheath could be removedafter the implantable device 4110 is placed in the desired position.These sheaths could incorporate bends or other curves (e.g. in aresiliently biased curved portion) to further improve thecontrollability and guidance of one or more portions of the implantabledevice 4110 as it is implanted.

In some embodiments of the implantable device 4110, the device 4110 iscapable of mechanically interacting with tissue, inducing motion in thesurrounding tissue, moving, rotating, squeezing, expanding, and/orrepositioning itself. This motion could be in the form of vibrations,impulses, linear displacements, and/or angular displacements. Thesemotions could assist (i.e. used in conjunction with) and/or replaceelectrical neuromodulation of nerves, muscles, and/or other tissues. Theequivalent of a stimulation pulse could be applied by a specificduration of vibration and/or displacement, including a displacementoffset with vibrations applied in addition. This stimulation deliverycould be performed at both low and high frequencies ranging from 1 Hz to50 kHz and with controllable duty cycles. Additionally, the waveform canbe custom designed or irregular in shape to produce the most effectivestimulation. A depiction of possible mechanical motion waveforms areshown in FIG. 55. The motion itself can be accomplished with severaltypes of forces including electromagnetics forces, magnetic forces,piezoelectric forces, thermal expansion forces, and combinationsthereof. These force methods can be fully enclosed within the devicehousing 4200, and can apply the mechanical forces without electricalcontact with tissue. If used with a lead 4220, the lead body and/or tipcan incorporate one or more mechanical interfaces designed for thespecific method of force generation. The lead 4220 could be anchored orsutured to the specific site to ensure the precision of long-termtreatments. The lead 4220 could also incorporate methods of adjustingposition over time to reposition the device and/or interface at thedesired location or to improve comfort of the implantable device.

In some embodiments of the implantable device 4110, different lead 4220and/or electrode 4230 configurations can increase the flexibility andversatility of the treatment. Leads can be cylindrical in shape with avariable number of electrodes, including 4, 8, 16, or 32 connections(e.g. between one and 64 connections) as well as other numbers ofconnections. The electrodes can source and/or sink variable currents andcan have adjustable polarity. By controlling the voltages and polarityat the different points of contact, the current can be steered orotherwise directed in certain ways through tissue. This directing ofcurrent can be important for targeting specific tissue sites whileavoiding stimulation of certain other tissues. The leads 4220 and/orelectrodes 4230 could also be configured in the shape of a paddleelectrode, in which the electrical connections are arranged across aflat or curved surface. The number of connections could be much largerin a smaller area with this arrangement, including 1 to 64 or moreconnections depending on the intended use. In spinal cord stimulation,additional stimulation channels and the ability to control or directcurrent can precisely target the specific nerves experiencing pain whileminimizing stimulation to surrounding tissues. In peripheral nerveand/or peripheral field stimulation, multiple leads working in acoordinated way with controllable stimulation channels, polarity, anddrive currents offer flexibility in the overall coverage area and enablecross-talk among one or more leads 4220 and/or electrodes 4230. Thepatterns of placement of these leads 4220 also can influence thecoverage of the neuromodulation, and placing electrodes 230 10-50 cmapart across the back can offer effective treatment outcomes.Additionally, placing the electrodes 4230 in a square, rectangular,diamond, circular, elliptical, regular, and/or irregular pattern acrossthe back can also improve coverage of the modulation. A singleimplantable device 4110 can support multiple leads that are eitherintegrated together or connected as needed. These leads 4220 couldbifurcate from the implantable device 4110 and be guided to differentlocations within the body. Alternatively, the implantable device 4110could have one or more connection interfaces for other implantabledevices 4110, housings 4200, leads 4220, and/or electrodes 4230.Examples of possible arrangements of a device with multiple leads areshown in FIG. 56. These leads 4220 can be coordinated from a singleimplantable device 4110, or leads 4220 from separate implantable devices4110 can be coordinated together to achieve the desired result. Aconnection hub 4300 can also be used to connect together multipleimplantable devices 4110 and/or multiple leads 4220 (e.g. multiple leadsconnected to one or more controllers). These connection hubs 4300themselves could also be connected to additional connection hubs 4300 toscale the overall system 411 to accommodate additional leads 4220. Inone implementation of a connection hub 4300, the hub acts as a binarysplitter, doubling the number of potential connection interfaces witheach stage of hubs. An example of a housing with one or more connectionsand a connection hub 4300 is shown in FIG. 57. Leads 4220 and/orimplantable devices 4110 could also be connected end to end toaccommodate a variable number of leads 4220 and/or electrodes 4230 andadditional separation distance of the stimulation sites. For sometreatments, it may be necessary to place electrical connections veryprecisely at specific nerve sites. The device 4110 can incorporatemicroelectrodes, which are small, independently positioned electrodesthat are precisely placed and connected to desired tissue. Theseelectrodes can be wrapped around the site and/or anchored in closeproximity of the site. These microelectrodes can protrude from a lead220, the implantable device 4110, or the device housing 200. Eachmicroelectrode can be independently controlled, and a set ofmicroelectrodes can be coordinated to offer a better treatment. Forstimulation of the dorsal root ganglion and many other specific tissues,it can be very important to precisely apply stimulation to avoidstimulating other nearby nerves or tissues. In some cases, the devicehousing 200 itself can include feedthroughs that directly connect to thedesired tissue. An example of this setup is shown in FIG. 54. The devicehousing 4200 can include one or more connections depending on its sizeand the feedthrough technology used. Some specific embodiments ofmicroelectrodes and tissue interfaces are described in U.S. ProvisionalPatent Application No. 62/015,392, titled “Methods and Apparatus forNeuromodulation Treatments of Pain and Other Conditions,” filed on Jun.21, 2014.

In some embodiments of the implantable device 4110, additional designfeatures to improve MRI compatibility can be incorporated, such as anMRI effect reducing assembly as described herein. The primary concernsassociated with MRI compatibility may involve the forces applied tomaterials by the magnetic field and induced currents in the device. Inmost embodiments, materials that experience forces in a magnetic fieldwill not be part of the implantable device 4110 or will be minimallyused so as not to cause issues. To mitigate the effects of inducedcurrents, heat sinks and/or heat spreaders can be included, shieldingcan be applied to the implantable device 4110, the lead 4220, and/or anylong wires or conductors in the implantable device 4110, and/or theaddition of active or passive shorts or other methods of divertingcurrent (e.g. near the lead tips). Heat spreading can be accomplished byusing materials with high heat conduction (e.g. via a high heatconduction element) in the areas where heating is most prevalent. Ashort can be introduced by a reed switch or a mechanical switch that isactivated before and/or during MRI use. Additionally, other parallelelectrical connections or current diversions can be introduced bymechanical switches, active methods, or passive methods to dispersecurrent and mitigate harmful effects on tissue.

In some embodiments of the implantable device 4110, additional designfeatures are incorporated in the leads 4220, electrodes 4230, and/orother electrical connections to reduce resistance and/or powerconsumption. This reduction can be accomplished with large wires,multiple wires in parallel for a single connection, and/or shorterwires/distances from the stimulator to the stimulation site. Lowerresistance materials can also be used to reduce resistance, andelectrode coatings, such as platinum, iridium, gold, alloys of thesemetals, such as Pt_(x)/Ir_(1−x), and other metal alloys, and/or carbonnanotube coating, can improve the connection with tissue and reduce theoverall impedance of the connection. Multiple channels can alsocoordinate to reduce the overall need for stimulation, which can alsoreduce the electrical current required for a desired therapy.

The implantation procedure can vary with indication. However, regardlessof the indication, an implantable device 4110 generally should bedelivered to a location inside of a human body as quickly and as safelyas practical. The specific location is determined based on indication,patient-specific conditions and preferences, anatomy, origin ofpathology, physician experience and preferences, and other variables ineach particular case. In order to accommodate some of these variablesand various device embodiments, the implantation procedure can beassisted with standard tools that are commonly used in the art. In someembodiments however, novel, customized tools are used for implantationof one or more portions of the implantable device.

For example, when implanting a lead for spinal cord stimulation, commontools, techniques, and procedures can greatly simplify the process.Common tools used for lead implantation are: anchors, extensions,needles (˜15 gauge, epidural, curved or modified Tuohy), stylets (withbent tip between 10-30 degrees, straight, short, soft, hard), tunnelingtools (rods, tips, tube), and others. Also, customized tools or toolsadapted from other indications can be used to improve implantationprocedure and give operating physicians additional flexibility andoptions. For example, insertion tools can be used in place of a needleto guide lead 4220 implantation. Example of an insertion tool that canbe used is described in U.S. Pat. No. 8,452,421 B2 “Lead InsertionTool,” which is designed for cochlear implant lead insertion, but can beadapted for use in other indications, such as spinal cord stimulationlead implantation. In one embodiment, a lead would be pre-loaded with amost commonly used stylet 250 in a package or kit. The operatingphysician would use a supplied insertion tool or a needle. The roughprocedure for lead implantation for SCS is outlined in the followingsteps:

1. An incision is made at the lead insertion (lead entry) place to thedepth of subcutaneous fascia.

2. Insert supplied needle or insertion tool using a paramedical approachand using imaging modality to guide the insertion. Imaging modality,such as fluoroscopy can be used to guide the insertion. Insert theneedle into the epidural space at the appropriate angle until someresistance is encountered from the ligamentum flavum. Preferably, theplacement of a lead is not at midline but to either side of the midlinebecause the ligament or spinous process movement can damage the leadover time. The needle or insertion tool should be inserted using ashallow needle-insertion angle (<45°) into the epidural space to reducethe risk of lead damage.

3. Confirm the needle or insertion tool placement using imaging. Adjustas necessary.

4. Rotate the needle or insertion tool such that the angle of entrywould as desired. In case of a needle, rotate the needle so that thebeveled edge faces the cephalad, remove the needle stylet.

5. Advance the needle or insertion tool and confirm entry into theepidural space using known techniques. For example, loss-of-resistancetechnique with air or sterile [United States Pharmacopeia—USP] water canbe used to confirm the entry. Use of flush or liquids, such as contrastmedia or saline flush, which would obstruct view or complicate furtherprocedures is not recommended.

6. Using imaging, slowly insert the lead through the needle and advancethe lead to the initial target placement site. A stylet may need to bereinserted. Use marking on stylet to determine angle of bending onstylet (when bent tip stylet is used). For example, the bent stylet canbe keyed on the stylet handle with key corresponding to same or oppositedirection of the distal bent tip, depending on the stylet used. Ifresistance is encountered when using bent stylet during leadadvancement, exchange the bent stylet for the straight stylet and useshort, firm movements to advance the lead.

In some embodiments, a guide wire can be used in addition or instead ofa stylet 4250, prior to lead advancement. A guide wire would make atrack for a lead to follow. That way, a guide wire is inserted first andis guided using an imaging modality until it reaches the desired placewhere the lead electrodes 4230 need to be positioned. Then the guidewire would be removed and a lead 4220 would be inserted. The lead wouldfollow the tracks made by a guide wire more easily. A stylet 4250 or aninserting sheath 4270 can also be optionally used with the lead 4220insertion.

In some embodiments, a guiding sheath 4270 or tube can be used to guidelead 4220 implantation. The sheath 4270 could be more rigid than a lead4220 and could have a curved end. The procedure would be similar to theearlier described procedure, with the exception of using of thedescribed sheath 4270 for lead 4220 advancement. After the lead 4220insertion and confirmation of the correct location, the sheath 4270 isremoved, leaving the lead 4220 and electrodes 4230 in place.

In some embodiments, a combination of sheath, stylet, guide wire and/orother filament 4250 is used for lead 4220 implantation. A sheath 4270with a guide wire acting as a stylet 4250 can be used to deliver thedistal end of the tube (sheath) 4270 to the correct location. The guidewire 4250 would then be removed from the sheath 4270. The lead 4220would then be inserted into the sheath 4270 and slidingly advanced untilit reaches the desired location. The sheath 4270 could then be removed,leaving the lead and the electrodes 4230 in the correct place for thedesired therapy. The sheath 4270 would have a narrowed distal end 4271to ensure the guide wire 4250 does not extend beyond the distal end ofthe sheath 4271. The diameter of the narrowed distal end 4271, however,is large enough to allow its removal after lead is inserted but smallenough not to let the guide wire through, as shown in FIG. 62. The guidewire in this case has very similar functionality to a stylet 4250.Therefore, it is important to have multiple options for the guide wire4250. The guide wire 4250 can have varying parameters to accommodatemore flexibility during the surgery. These parameters include: rigidity,length, diameter, curved or straight, bent tip.

The sheath 4270 could also accommodate (e.g. provide support for) theusage of a camera (such as fiber optic camera including a visible lightfiber), ultrasound fiber, sensing lead, and other tools that can furtherbe used during lead 4220 implantation and can help in determining thecorrect or the best location for the lead 4220 and electrodes 4230. Forexample, a lead 4220 with a sensor (e.g. sensing electrodes) can be usedwith sheath 4270 during lead advancement. In some embodiments, thesheath 4270 includes one or more sensors. The sensors can be used tomeasure action potentials, neural activity, and/or muscle activity tohone in on the right location. Other sensors and/or transducers can beused (e.g. included in the lead 4220 and/or sheath 4270), such as tomeasure one or more of pressure, temperature, pH, and others.

In some embodiments, a sheath 4270 with lead 4220 and stylet 4250 areinserted and advanced until they reach the desired location. After theelectrode 4230 reaches the desired location, the sheath 4270 can beremoved and the lead 4220 can be adjusted and further advanced using thestylet 4250. The stylet 4250 could then be removed, leaving the lead andelectrodes 4230 in the correct location for the desired therapy.

Several embodiment options for lead which can accommodate a stylet areshown in FIG. 60. Also, several options of a lead cross-section areshown in FIG. 61. As can be seen from the figures, the lead 4220 wouldinclude a lumen 4260 through which a stylet 4250 can be inserted. Thelumen ends at the distal end of the lead 4221, such that the stylet,effectively, pushes the lead due to its rigidity. The lead 4220 can becircular, oval, rectangular, or other shape in cross section. Also, thestylet lumen 4260 (or lumen which can accommodate other things asidefrom stylet) can have various cross section shape, depending on therequirements, and can be circular, oval, rectangular, or other shapes.The cross-section also shows insulated conductors 4310 which connectelectrodes 4230 to active circuitry (electronics) 4241. The conductors4310 can be of various types and implemented in various ways. Forexample, in some embodiments, the conductors 4310 can be implemented ona flexible PCB, can be individual insulated wires, multi-stranded wires,bundles of wires, single strand wires, magnetic wires, and otheroptions. FIG. 60 shows several different embodiments of the implantabledevice 4110 comprising a lead 4220 with electronics 4241 and one or moreantennas 4240 built into the lead (e.g. entire implantable device 4110is in a lead form factor) or electronics 4241 encapsulated in a sealedpackage or housing 4200 on proximal end of the lead 4220. In thefigures, the lead comprises one or more insulated conductors 4310 andone or more lumens 4260. The conductors 4310 connect electrodes 4230 tothe active circuitry 241 that drives stimulation waveforms through theelectrodes 4230. The one or more lumens 4260 can be used to accommodatea stylet 250 or other tools that can be used to aid with the leadimplantation procedure.

As described in previous sections, some embodiments of the implantabledevice 4110 comprise one or more leads 4220, possibly bifurcated leads,connected to a sealed package or housing 4200 that houses active and/orpassive circuits 4241, antennas 4240, and other components. In case theencapsulation or housing 4200 (e.g. hermetic encapsulation) is not fullyintegrated into a lead 4220, the sealed housing 4200 can protrude beyondthe diameter of the lead. In order to accommodate minimally invasiveimplantation without surgery, it is important that implantation tools donot block doctor's view of lead entry point and also provide for easymanipulation during lead 4220 and device housing 4200 implantation. If aneedle 4510 is used for lead implantation, as described in the stepsabove, a doctor would need to have an ability to remove the needle 4510without removing the housing 4200 from the lead 4220 (i.e. in case thehousing 4200 is not connectorized to the end of the lead 4220). In orderto accommodate needle 4510 removal post lead implantation and to allowfor device housing 4200 to be implanted, the needle 4510 can consist ofseveral parts. Some embodiments of the introducer needle are shown inFIG. 71 and FIG. 72. As shown in the FIGS. 71, 72, in some embodiments,the needle 4510 can consist of two parts which are held together with ahinge 4511 that unfolds or breaks apart, or surrounding tube or sheath(similar to shrink wrap tube) 4512 which is biocompatible. The sheath4512 can be silicone, plastic, or other similar materials. After lead4220 implantation procedure is complete, the sheath 4512 can be cutenabling the two parts of the needle 4510 to come apart, which could beassisted with perforations along the sheath. Then, the rest of thedevice package or housing 4200 can be implanted under the skin.

In other embodiments, the lead 4220 can be connectorized to the sealedhousing 4200, such that the lead 4220 can be separately implanted usinga needle 4510 or insertion device. The needle 4510 would then be removedand the housing 4200 would be connected via connector interface 4210 tothe lead 4220 for implantation, allowing a physician to complete theimplantable device 4110 implantation procedure.

Some form of anchoring can be used to ensure permanent implantation ofthe implantable device 4110 by securing or fixating it in place. Atleast a portion of the implantable device 4110 can be sutured to fix itin place. The implantable housing(s) 4200 can contain built-in eyeletsor other suture holes 4280 for sutures. Alternatively, or in addition toeyelets, barbs, staple; fixation parts and/or other anchor elements canbe added to the lead 4220 and/or other portion of the implantable device4110 to serve as additional spots for suturing and permanent fixationwithin a patient prior to closing the incision spot. These anchorelements 4281 can comprise a texturized pattern for improved grip suchthat they do not slide along the lead 4220 or device housing 4200 andsuch that sutures would not slide along the anchor 4281. This anchoring4281 would effectively enable the sutures to fix the device and/or leadin place permanently. Other anchoring elements 4281 can be in shape of aclamp that can clamp around a lead and/or device. Sutures or staples canbe used to close the clamp and prevent it from opening after theimplantation and fixation procedure and to hold the device in place. Theclamp would contain an extension with one or more holes 4280 for suturesto be inserted through as can be seen in FIG. 63.

As previously described, in order to determine the implantable device4110 position and orientation, an imaging modality can be used.Radio-opaque or other visualizable markers at the lead tip (e.g. distalend of the lead) 4221 can be used to help identify the lead 4220 andelectrode 4230 position with regard to the anatomy. Furthermore, imagingcan be done from multiple different views, such as anterior-posteriorand lateral views, in order to determine the 3-D position andorientation of the lead 4220 and the electrodes 4230. In someembodiments, several radio-opaque markers are included (e.g. on and/orin the lead 4220) with certain predetermined shapes and inpre-determined locations along the lead 4220, such as at the distal endof the lead 4221, in order to further simplify the orientationprocedure. For example, if the perceived shape of one or more markerschanges with device position, rotation, and orientation, fewer imagingviews can be used to establish the 3D position of a lead 4220.Appropriate shape for a visualizable marker can be selected such thatit's projection on a 2D plane would reveal additional information aboutdevice rotation, tilt, and orientation. FIG. 70 shows several differentexamples of such visualizable markers in different orientations,rotations, and positions. From the figure, it can be seen that if animplantable device 4110 which includes such visualizable marker isrotated or tilted, the 2D projection of the imaged marker would change.Thus the device position, orientation, rotation, tilt, and general 3Dlocation can be more easily determined with fewer steps, simplifyingprocedure and reducing the number of images that need to be taken duringthe procedure. The radio opaque markers can also include the device IDfor easy retrieval during implantation, warning labels, and othermarkers that can be used during implantation, programming, routine use,explanation, servicing, etc.

In order to determine the correct location of the lead 4220 and toensure that the electrodes 4230 are located in proximity to the nervesor anatomic site that needs to be activated or suppressed viastimulation waveform, the overall system 411 may need to be testedintraoperatively. This testing involves activating the implantabledevice 4110 and stimulating tissue. During this intraoperative testingor trialing, the patient can be required to provide feedback about thesensation of paresthesia, its location and/or comfort level, for avariety of stimulation parameters and/or electrode configurations. Inorder to ease with this intraoperative trialing, a special trialinginterface 4400 is included in the overall system 411. Since theimplantable device 4110 would not be fully implanted yet, the trialinginterface 4400 can be of a different configuration than the externalpatch or other external device component that would normally be used toactivate one or more implanted portions of the implantable system of thepresent inventive concepts. Some example embodiments of theintraoperative trialing interface 4400 are shown in FIG. 64 and FIG. 65.

In some embodiments, the trialing interface 4400 comprises a dockingelement 4410 (or docking port) which would house or otherwise at leastpartially surround the at least a portion of the implantable device4110, such as to surround a proximal end of a lead, such as towirelessly couple to the implant. The docking element 4410 can fitsecurely to ensure that the wireless link quality is acceptable and doesnot vary significantly with surroundings. The shielding from thesurroundings can be accomplished by incorporating radio absorptiveand/or radio reflective materials 4411 into the construction of thedocking element 4410. The doctor could then manually adjust stimulationparameters until a desired set of parameters is determined and/or anacceptable lead 4220 and electrode 4230 location is established.Alternatively, the trialing interface 4400 could incorporate a specialsearch algorithm that would step through the stimulation parameters andbased on patient feedback or automatically find the proper set ofstimulation parameters. Based on the trial and/or patient feedback, thelead 4220 location may need to be readjusted and trialing redone. Afterit is determined that the location of the lead 4220 and electrodes 4230is proper, the implantable device 4110 can be fully implanted, securedin place and the incision closed up.

In some embodiments, the trialing interface 4400 can be connectorizedwith mating connectors (e.g. electrical connectors) 4210 on the trialinginterface 4400 and associated portion of the implantable device 4110(e.g. lead 4220 or device housing 4200). This wired trialing procedureis similar to the wireless trialing procedure, but with a wiredinterface 4210. The trialing connector 4210 can be configured to matewith a lead connector 4210 of similar construction to a connectorizedsealed housing 4200. Alternatively, the trialing interface 4400 can matewith a connectorized antenna interface. In the case of a lead interface,the trialing interface 4400 would directly drive electrodes 4230 throughthe leads 4220 and therefore would have to drive stimulation waveformsout of a waveform generator, similar to the functionality of theimplantable device electronics 4241. However, in case when a trialinginterface mates with a connectorized antenna interface, the trialinginterface 4400 would have to mimic RF signal transmission that wouldnormally be received wirelessly during normal operation. Therefore, thetrialing interface would include an RF carrier modulated with data butwould excite the input to the electronics 4241 of the implantable device4110 in a wired way. The trialing interface could have its own matchingnetwork which matches to the same carrier frequency that would normallybe used during operation or to a different frequency. Operation at lowerfrequency can be advantageous for power savings and lower complexity ofthe trialing interface, since the size of the trialing interface is notconstrained as much as that of an implantable device 4110.

For certain applications that require deeper implants, higher powerbudgets, more stringent size requirements for the external battery,and/or link gain improvement, it can be beneficial to have the antennaor multiple antennas located closer to the skin surface than one or moreremaining portions of the implantable device, as shown in FIG. 64 andFIG. 65. In order to accommodate this placement configuration, theimplant antenna or antennas 4240 could be connected to the rest of theimplant or implant housing 4200 with a connecting interface or otherconnecting element, such as cable, wires, conductive leads, transmissionlines, waveguides, distributed matching network, transformer, lumpedmatching network, or other configuration (hereinafter interconnect) 4310that allows for the antenna(s) 4240 be separate from the active and/orpassive circuits enclosure 4200. The interconnect 4310 between remoteantenna 4240 and the rest of the implantable device can thus act as amatching network or simply an electrical connector. The interconnect4310 can be flexible, rigid, semi-rigid or include at least a flexibleportion, and it can be used to position the antenna(s) 4240 independentof the rest of the implantable device. The resulting remote antenna orpig-tail antenna 4240 can be positioned at a location within the body ofthe patient that optimizes link gain. Furthermore, multiple antennas canbe connected this way to the rest of the implant. The position of eachantenna can be individually adjusted to optimize link gain for a varietyof situations and operating conditions. For example, several antennascan be distributed under the skin to make the link gain less sensitiveto external device position (e.g. external patch position), relativeorientation, alignment, and/or rotation as shown in FIG. 64 and FIG. 65.Furthermore, one or more remote antennas 4240 can be foldable andunfoldable to enable minimally invasive implantation as described inU.S. Provisional Patent Application No. 61/953,702. Alternatively, or inaddition to this, the antenna extensions (i.e. individual remoteantennas 4240) can be positioned orthogonally with respect to each otherto further desensitize link gain to the position of one or more externaldevice components (e.g. less sensitive to external patch or externalantenna 4150 positioning). The remote antenna 4240 physical structurecan be optimized for a particular application and can be selected fromthe list of: loop antenna, multi-loop antenna, orthogonal antennas,polarized antenna structures, dipole antenna, multi-coil antenna,helical antenna, patch antenna, and combinations thereof.

In some embodiments, one or more remote antennas 4240 can connect to therest of the implantable device with feedthroughs, resulting in apermanent configuration. In some embodiments, the rest of theimplantable device and one or more of the remote antennas can havemating connectors 4210. The connectors 4210 can be standardized suchthat the same core implantable device housing 4200 can be mated with aspecific antenna 4240 that is best optimized for a particular need,indication, use, and/or operating environment. The antennas 4240 couldhave a specific impedance that would be matched and/or resonant with acomponent of the implantable device 4110 (e.g. the electronics 4241housed in a package or housing 4200) at a particular frequency in orderto maximize performance. Alternatively, or in addition to this, aninterposer matching network 4300 a can be used between the antenna 4240and the housing 4200 (FIG. 69). The interposer 4300 a could furtherinclude combiners, splitters, and other radio frequency (RF) componentsto further optimize link gain and make the design of implant electronics4241 and antennas 4240 more flexible and versatile. With this approach,several antennas 4240 can be supplied with the implantable device 4110and an operating physician could have a choice of the antenna 4240 toimplant in a particular patient to accommodate a particular situation.Similarly, a physician can select an appropriate lead 4220, from severaldifferent leads which can be supplied with the implantable device 4110,for a particular situation.

A connectorized interface 4210 for one or more swappable antennas 4240further offers additional benefits and flexibility. Firstly, itaccommodates multiple antennas 4240 to suit a particular need withouthaving to redesign the whole implantable device 4110. Furthermore, otherdevices and components (extension devices 4301) can be connected to theimplant to improve functionality, utility, and/or accommodate differentuses. For example, a testing assembly can comprise a power supply suchas a battery with a special RF interface that mimics an antenna 4301 canbe connected to the implant if application requires for the use of abattery. The RF interface would be designed to provide a signal to theimplantable device according to what would be expected at the output ofthe antenna. The battery could be beneficial for certain applications,such as when external patch is not a viable or at least not a preferredoption. Other attachment elements 4301 could include a trialinginterface 4400 for intraoperative trialing as shown in FIG. 64 and FIG.65.

Similar to connectorized antennas, in some embodiments, it can bepreferred to have connectorized lead/electrode interface on theimplantable device (e.g. a sealing connector) as shown in FIG. 67. Aconnectorized lead interface would enable for a simpler implantationprocedure as described herein. Also, a connectorized lead interface 4210provides higher flexibility in adapting the implant to a particular caseto meet the therapy requirements. For example, leads of various lengths,diameters and other dimensions, electrode shapes, electrode sizes,electrode configurations, and other lead variables can be accommodatedwith the same device as long as the connectors are designed to mate toeach other. For example, with a connectorized lead interface, the sameimplant housing 4200 can be used with a variety of leads 4220, such ascylindrical leads, paddle electrodes, microelectrodes, bifurcated leaddesigns, and other lead options. Also, similar to the connectorizedantenna interface, connectorized lead interface can mate with a varietyof optional devices and/or adapters, such as splitters for leads; activeand/or passive interfaces for leads, such as serializer and/ordeserializer for active leads; lead extensions; diagnostic interfacesthat can be used to test implant functionality at any point during thelifetime of the device. Other interposer components 4300 a and/ordevices can also be used by mating with the implant housing 4200 andleads 4220, such as a charge balance device, pulse conversion or pulseshaping device (e.g., DC to pulse burst), filters, etc. As was mentionedbefore, all these connecting devices or attachment elements, can bepassive—such as leads or splitters, passive filters, AC-couplingcapacitors for charge balancing, active—such as pulse conversiondevices, active filters, active charge balancing circuits, orcombinations thereof.

In some embodiments, it can be beneficial to connect active or passivedistribution circuits or hubs to the connectors 4210. These distributioncircuits can distribute stimulation and/or sensing channels from thedevice to remote electrodes which can be placed in various locationsthroughout the anatomy of a patient. These distribution circuits cancomprise splitters and/or hubs which interface with one or moreconnectors on the implantable device 4110 and one or more leads. Eachlead 4220 would have one or more electrodes 4230. This way, theconnector interface 4210 on the device housing 4200 can be standardizedbut the leads 4220 can be customized to a particular application withthe distribution circuit acting as an interposer or adapter 4300 a.Unused connectors can be deactivated through active control of theimplantable device 4110 or can be blocked with a termination plug 4302to prevent the connector from contacting the tissue once the implantabledevice 4110 is implanted. These connectors 4210 can be placed in variouslocations on the implantable device 4110 or implant housing 4200, suchas next to each other, on opposite ends of the implantable device 4110or implant housing 4200, or distributed throughout the implantabledevice 4110 or implant housing 4200.

In some embodiments it can be beneficial to have multiple electrodes4230 distributed throughout the body that can provide cross-talk or cansteer current from one electrode to another remote electrode in adifferent location of the body. In that case it is necessary for theelectrodes 4230 to have a common reference node which requires theelectrodes to be physically connected to the same active deviceelectronics 4241 with one or more channels. In order to enable thisconfiguration, bifurcated leads can be used which are connected to thesame implantable device 4110 or same device housing 4200. Also, it canbe beneficial to network multiple leads in series to enable all theimplanted portions to have a common reference node. In thoseconfigurations, active leads can be used which can send and/or receivecommands from one implantable device (e.g. single electronicsencapsulating package or housing 4200). A serial communication link withone or more conductors can be used in those configurations. A serialprotocol can be used to control these active leads 4220. However, theleads 4220 would have to support this serial protocol. A low powerserial interface with connectors 4310 for power, ground, and one or moreserial data wires can be used in those configurations. The leads 4220can have connectors 4210 on both ends of the lead 4220 to enable seriesconnection of one lead to the next in a chain. Each lead could have itsown ID code (e.g. an addressable code) and a single controller (e.g.electronics 4241 housed in a package or housing 4200) can program eachlead 4220 through the serial communication interface independently,collectively, or in coordinated manner. This concept is illustrated inFIG. 69. Similar to what is described hereinabove, unused connectors4210 can be closed with a termination plug 4302 in order to prevent theconnector 4210 from coming in contact with tissue, which couldpotentially damage the lead 4220 and/or connectors 4210 over time. Thetermination plug 4302 can be configured to keep the connector 4210contacts sealed.

In some embodiments, multiple implantable connectors 4210 can comprisewired connectors with conductive contacts, as normally used with activeimplantable devices. Alternatively, a connection interface 4210 can beAC-coupled and even wireless. In some embodiments, an implantable device4110 (e.g. encapsulation package or housing 4200) does not includefeedthroughs or a wired connector interface 4210. Instead, the connectorinterface 4210 is wireless. In a wireless connector interface 4210,connectors do not use conductive interface between the encapsulatedpackage (e.g. hermetically encapsulated package or housing 4200) andextensions 4301, such as antennas 4240, leads 4220, and other possibleextension devices as described hereinabove. Instead, signals are coupledand transmitted wirelessly. Absence of feedthroughs can be advantageousfor fabrication and/or life expectancy of the implantable device 4110(e.g. feedthroughs may result in a limited life). Examples of wirelessinterfaces or AC-coupled interfaces 4210 are described below. In someembodiments, an AC-coupled interface 4210 relies on one or moretransformer coils 4211 which form one or more transformers with aprimary transformer coil 4211 located inside the package or housing 4200and a mating (complementary) secondary transformer coil 4211 located inan extension 4301 (such as a lead 4220 or antenna 4240). Depending onthe number of turns in each primary and secondary transformer coils4211, this configuration could further enable voltage/current step up orstep down, thereby increasing the interface utility. The transformercoils 4211 can be planar coils in the implant housing 4200 with matchingset of planar coils in the extension devices 4301. Alternatively, thetransformer coils 4211 could be coplanar coils. In that case, theimplantable device package or housing 4200 can have a concave or convexport 4212 which would mate with an extension device port, as shown inFIG. 58. As shown in the figure, in one embodiment, a lead 4220 can beinserted into a port 4212 in sealed housing 4200, aligning all theco-planar transformer coils 4211. Each electrode 4230 can have anassociated set of primary and secondary coils 4211 which are inductivelycoupled. . This AC-coupling interface 4210 can comprise a frequencyresponse which accommodates the required stimulation waveforms withoutunintended filtering. This similar concept of an AC-coupled interface4210 can be applied to a wireless antenna connector. Because the antenna4240 normally only supplies RF signal, this interface 4210 is even morepractical for antennas 4240 use because smaller transformer coils 4211for coupling can be used for RF. Ferrite cores can further be used withthis transformer-based interface 4210 to further improve coupling and/oradjust frequency response.

In some embodiments, the AC-coupling interface 4210 can be implementedusing capacitive coupling. The capacitors are formed in a similar mannerto inductive wireless interface—by aligning a conductive plate 4213 onimplantable device housing 4200 with a plate on extension device 4301(such as lead 4220 or antenna 4240)—which would form pairs of parallelplates. Some embodiments of the capacitive AC-coupled interface areshown in FIG. 59. The encapsulation between the plates (e.g. capacitordielectric 4214) can be the same as the rest of the encapsulation or canbe selectively made of a material with different dielectric constant, κ.For example, high-κ dielectrics would result in higher capacitivecoupling and thus smaller area plates 4213 can be used. Also,encapsulation 4214 can be selectively thinned around (e.g. between) themating plates 4213 to further increase the capacitance. In someembodiments, the extension device plates 4213 are not encapsulated toreduce the distance between the plates 4213 and increase capacitivecoupling. The exposed plates 4213 can be plated with or made ofmaterials that are biocompatible. This construction would not increasethe risk of oxidation or corrosion because these nodes are only exposedto AC signals and not DC signals. This type of coupling is alsoadvantageous because it results in charge balancing circuitry withoutexplicit use of discrete AC-coupling capacitors, which enables furtherminiaturization by reducing number of passive components used in theimplantable device 4110.

As was mentioned before, there are multiple ways the implantable device4110 can be encapsulated and packaged. The actual method ofencapsulation and packaging depends on the intended application, becauseof the tradeoffs involved with each choice. For example, siliconeelastomers, such as Silastic, are typically flexible and inert tobiological tissue interactions but are permeable with liquids commonlyencountered in implantable applications. Therefore, devices that areencapsulated with Silastic or similar silicone elastomers have a shorterlifetime than device that are encapsulated with less permeableencapsulation methods, such as fluorocarbons, crystalline materials,glass, ceramic, or metal packaging methods. The tradeoff with the lesspermeable encapsulation choices is that they can require feedthroughsfor conductive connections which increase the device size withincreasing number of feedthroughs due to a fairly low density offeedthroughs. Additional consideration of choosing a less permeablematerial is the ability of the material to pass the desired wirelesssignals through the package without significantly attenuating them. Forexample, metals significantly attenuate electromagnetic waves in a verybroad range, including RF and optical range. Therefore, using RF powertransfer and RF or optical communication techniques with devices thatare encapsulated or enclosed in metal packaging presents additionalchallenges due to signal attenuation. Glass, ceramic, some nonmetalliccrystalline materials, fluorocarbons, and silicone materials do notattenuate electromagnetic waves as much as metals do. Therefore, the useof these materials for encapsulation would be significantly moreadvantageous to metal encapsulation when implantable devices rely onwireless powering and communications. Other material properties, such asflexibility, resistance to mechanical stress, and other properties needto be accounted when selecting materials for implantable deviceencapsulation and packaging.

In some embodiments, the implantable device 4110 or at least parts orelements of the implantable device are packaged in a sealed (e.g.hermetically sealed) cylindrical or planar glass encapsulation orhousing 4200 with high density feedthroughs 4201 to connect to one ormore electrodes 4230 and/or one or more antennas 4240. One of the keyadvantages with this encapsulation method is that the implantablepackage or housing 4200 does not attenuate electromagnetic waves, so inconfigurations in which an antenna 4240 is enclosed within the packageor housing 4200, the implantable device 4110 can be powered and cancommunicate using an RF carrier. Additional benefits are: longerlifetime due to sealed packaging; robust package design which is notsusceptible to fractures due to mechanical stress; high densityfeedthroughs 4201 enable multi-channel and/or multi-electrode therapyand/or diagnostics (sensing); small form factor of the package enablesminimally invasive implantation and comfort for patient; significantreduction in implantation time because tunneling is not required for thesmall form factor package. Several embodiments with cylindrical andplanar glass encapsulation technology are shown in FIG. 48, FIG. 49, andFIG. 50. The glass substrate is also bio compatible and bio-stable. Theglass substrate can further be encapsulated with silicone or similarcompound and overmolded if necessary.

In other embodiments, the implantable device 4110 can be fullyintegrated into a lead 4220 with electrodes 4230. In those cases,elongated antennas 4240, such as dipole antenna, elongated loop ormulti-loop antenna, can be used and can extend along the lead for alarger cross section. Flexible or rigid PCB substrate 4202 can be usedto mount electronic components 4241 such as ASIC and other discretecomponents along the length of the lead 4220. The PCB 4202 can containconductors 4310 to electrically interconnect the electronic components4241, one or more antennas 4240, and electrodes 4230. The lead 4220 canbe made of a variety of biocompatible materials, including a variety ofpolymers such as polymethymethacrylate (PMMA), polydimethylsiloxane(PDMS), parylene, polyurethane, polytetrafluoroethylene (PTFE),polycarbonate, and other similar compounds. The form factors can besimilar to what was previously described and shown in FIG. 51.

The one or more external devices 4100 and the one or more implantabledevices 4110 can work individually or coordinate in a network to treat avariety of conditions. The one or more implantable devices 4110 can beplaced in one or more of the following sites for sensing and/ortreatment: the tibial nerve (and/or sensory fibers that lead to thetibial nerve); the occipital nerve; the sphenopalatine ganglion; thesacral and/or pudendal nerve; target sites in the brain, such as thethalamus; the vagus nerve; baroreceptors in a blood vessel wall, such asin the carotid artery; along, in, or proximal to the spinal cord; one ormore muscles; the medial nerve; the hypoglossal nerve and/or one or moremuscles of the tongue; cardiac tissue; the anal sphincter; peripheralnerves of the spinal cord, including locations around the back; thedorsal root ganglion; and motor nerves and/or muscles. The overallsystem 411 can be used to treat one or more of the following: migraine;cluster headaches; urge incontinence; tremor; obsessive compulsivedisorder; depression; epilepsy; inflammation; tinnitus; high bloodpressure; pain; muscle pain; carpal tunnel syndrome; obstructive sleepapnea; pace or defibrillate the heart; dystonia; interstitial cystitis;gastroparesis; obesity; fecal incontinence; bowel disorders; chronicpain; improving mobility; SCS for heart failure.

The following describes challenges and approaches to of ensuring chargebalance safety in an SCS application while minimizing the size penaltyof DC-blocking capacitors, which may be applicable to many embodimentsof the present disclosure.

In conventional neurostimulators, DC-blocking caps are generally placedin circuit between any active electronics and each (or all but one)electrode. The object of the capacitors is to prevent any net DC currentflow through tissue, which would otherwise cause irreversibleelectrochemical reactions at the electrode-tissue interface and resultin tissue damage. These capacitors generally perform two interrelatedfunctions:

A) During normal stimulation with fully functional electronics, thecapacitors can prevent net DC current through tissue that wouldotherwise occur due mismatches in the current sources or other non-idealcharacteristics of the electronics. Each capacitor may be in series withan electrode during both the stimulation (charge) phase and theopposite-polarity recovery (discharge) phase, so any net difference incharge transfer between the two phases cause a voltage to build upacross the capacitor. This voltage may ultimately cause thelarger-magnitude phase to go into compliance limit and thus achievescharge balance.

B) The DC-blocking capacitors may prevent tissue exposure to DC currentin the case of an electronics failure within the stimulator, such as aleaky IC pad, a stuck DAC bit, etc. The assumption may be that thesecapacitors would protect against any single-point failure; a multi-pointfailure that involves a capacitor itself would not be addressed.

The following sections discuss these two aspects of charge balance andDC protection, and approaches to eliminating the need for DC-blockingcapacitors. The schemes described below and herein may be applicable toany of the stimulation systems, devices, and apparatuses described aboveand herein.

1) P/NDAC Imbalance.

In theory, the typical ˜5% potential mismatch between P and N currentsources could be addressed by using an H-bridge-like configuration wherethe same P and N sources are switched between stimulating andindifferent electrodes in the two phases of a biphasic pulse. The weakerof the two sources may determine the current, so the only mismatchbetween the two phases should be due to the effective impedance of thecurrent source and the output DC bias delta over the course of the twophases. Cascoded current sources typically have effective parallelimpedances in the megohm range; e.g., for a 5 megohm source impedanceand a 5 V bias delta between the two phases, the resulting mismatch willbe 1 uA. Assuming a 1/20 pulse duty cycle (250 us pulse width at a 200Hz rate), the average current imbalance may be 50 nA. This may be intechnically below the 100 nA safety limit, but higher than desirable. Inaddition, if the stimulating and recovery phases of the biphasic pulseare asymmetric, then the INL of the DACs may also be a potential sourceof imbalance. INL can possibly be improved by creative DACarchitectures; e.g., if the DAC is composed of 4 equal sections, thesecould be switched so as to drive in parallel during the stimulationphase and sequentially during a recovery phase that is one fourth thecurrent and four times the duration of the simulation phase, so thateach section contributes the same amount of charge in each phase. In anycase, even with optimal current source design, a small residual chargeimbalance will likely exist after the biphasic pulse.

2) Shorting.

At first glance, shorting may seem like a good option to remove anyresidual charge imbalance for an SCS application, due to the longinterval between pulses relative to the time constant of theelectrode-tissue interface. Referring to the simplified electrode model7200 shown in FIG. 72 taken from Ji-Jon Sit's PhD thesis (Sit, Ji-Jon“An asynchronous, low-power architecture for interleaved neuralstimulation, using envelope and phase information” PhD Thesis, MIT,2007).

The electrode-tissue interface may comprise the double-layercapacitance, Cdl, the solution spreading resistance, Rs, and theFaradaic resistance, Rf. For a typical cochlear implant electrode, Cdlcan be in the 5-15 nF range and Rs in the 2-20 Kohm range, so an upperbound for the time constant to discharge Cdl through Rs is on the orderof 300 us. For SCS with a larger electrode, Cdl may be higher and Rslower, so it's probable that the time constant falls in a similar range.Thus with a 200 Hz pulse rate, there could be roughly 10 time constantsavailable to discharge Cdl through shorting, which again sounds like aneasy proposition.

A difficulty may be that during the biphasic stimulation pulse, somecurrent also passes through Rf. The Faradic resistance may be due toelectrolytic reactions at the electrode interface, which are not alwaysreversible, and are potentially destructive to tissue. At the end of thebiphasic pulse the net current through Rf is non-zero, even if the twophases are perfectly charge-balanced, since the net voltage across Rf isnon-zero. Thus if Rf is sufficiently small, shorting iscounter-productive, since it prevents Cdl from discharging through Rfand equalizing the Rf current. It can be demonstrated mathematicallythat for Rf is greater than 1 megohm, shorting should not present aproblem, and proposes using a shorting interval of about 3 timeconstants to remove ˜0.4% residual mismatch from his activecharge-balanced DAC design. The safety of this assumption may have to beverified experimentally.

3) DAC Linearity and Compliance Limits.

Even assuming well-balanced current sources and that shorting can beused to remove small residual charges, it may all fall apart if eithercurrent source approaches its compliance limit, since the resultingreduction in current output will not be balanced in the opposite phase.And from experience with cochlear implants, it seems likely that typicaluse cases will bump up against the compliance limit occasionally if notoften.

The chart 7400 in FIG. 74 below shows I-V performance of a cascoded PFETcurrent mirror, typical of the positive source of a stimulator output.At the left side of the chart, the current source is in compliancelimit, with output current starting to drop off at about 2V below VDD,and dropping off steeply at 1V. This is the current-source “dropout”voltage, and is one of the overhead power costs of a current-basedstimulator. To the right of the dropout voltage point is long flatregion, where effective output impedance is typically in the megohmrange. This is where the source needs to operate if we want to ensurecharge balance by means of the current source matching. To the right ofthe linear region the current starts to climb in an uncontrolled manneras the output devices exceed their breakdown voltage. This should beavoided in practice by use of correctly-specified high-voltage outputdevices and limiting maximum VDD.

One way to address the problem of compliance limits may be to add avoltage detection circuit at the current source output. When theapproach of compliance limit is detected, the current source can beturned off. This can either be treated as an error condition and haltstimulation, or if this occurs during the stimulation phase, the time atwhich detection occurs can be latched and used to reduce the duration ofthe recovery phase, so that charge balance is preserved. In order to dothis in a reliably safe manner, the detector may have to be veryconservatively specified, so that stimulation is stopped while outputvoltage is still in the linear range, accounting for process and voltagecorners. This might mean a detection point set at a volt or so higherthan the start of the dropout region, which means effectively anadditional volt of dropout. This may be ameliorated somewhat by the factthat the DC-blocking cap that such a circuit helps eliminate would alsocontribute to additional dropout (e.g., a 2.2 uF DC blocking cap willdevelop ˜1V across it during the course of a 10 mA current pulse of 200us duration.) So the efficiency loss due to an early compliancedetection point may turn out to be roughly a “wash” with the eliminationof the DC-blocking cap.

4) Simple Single-Channel Stimulator

In the case where only a single channel (electrode pair) is stimulatedat a given time, a single current source can be used in a H-bridgeconfiguration, with switches to a supply node forming the return path.This is shown in FIGS. 75a and 75b , with current paths 7500 a, 7500 bindicated for the stimulation and recovery phases. The same currentsource can be used for both stimulation and recovery, and so as long asits output bias voltage remains in the linear region, charge balancewill be close to optimal. (With the caveat and possible workaroundregarding INL if stimulation and recovery phases are asymmetric, asdescribed in 1) above.) Multiple single source H-bridges can beactivated together during the stimulation phase, and can be activatedsequentially during the recovery phase. This would require that each ofthe single current sources have a common sink (if driving from the highvoltage side) or a common source (if pulling from the low voltage side).

A few other notes about this approach:

As shown in FIGS. 75a and 75b , there may be one source switch and onegrounding switch for each electrode; these need to be physically largedevices to reduce series resistance. The good news, however, that isthat grounding switches at least may not need to be complementarytransmission-gate switches; NFETs alone should be sufficient.

As discussed in 3), above, charge balance can break down when thecurrent source goes into compliance and one mitigation is suggestedthere. Another option that retains some benefit of simplicity may be ahybrid approach using a single off-chip DC blocking cap that isavailable as common resource, and connected to the active electrodes byswitches, as shown in FIGS. 76a and 76b by circuit diagrams 7600 a and7600 b, respectively. This can solve the compliance issue, though notthe single-point-failure risk, which is discussed in subsequentsections. This approach may have the obvious cost of one large off-chipcapacitor, but is still much more compact than the traditional approachof one capacitor for each electrode.

If an off-chip DC-blocking capacitor is used, the relativevalues/volumes of the DC-blocking capacitor and the VDD bulk or “tank”capacitor should be considered. As it pertains to loss of compliancevoltage during the stimulation and recovery phases, the DC-blocking andtank capacitors can be effectively in series with each other, as bothdevelop a voltage drop as current is delivered to the load. For thisreason, trying to make the tank capacitor much larger than theDC-blocking capacitor may not be beneficial, and making them close toequal in value may allow a larger DC-blocking cap than otherwisepossible and a more optimal solution. For example, if both capacitorsare 4.7 uF, the total compliance loss over a 10 uA, 200 us pulse will be0.85 V. On the other hand, if the DC-blocking capacitor is 1 uF and thetank capacitor is 10 uF, the compliance loss will be about 2 V.

Finally, one thing that might need to be considered given that thestimulator will be driving a capacitive load: During the recovery phase,the more-positively-charged terminal of the load will be connected toground, and so the other terminal could initially go below ground andpossibly forward-bias ESD protection diodes, which will reduce theaccuracy of the current source. One possible way to mitigate that is tomake the grounding switch act more like a linear load; a simplifiedversion is shown by circuit diagram 7700 in FIG. 77.

5) Multi-Channel Stimulation

If there is a requirement to stimulate more than one channel (electrodepair) simultaneously, than the single-channel scheme above may notsimply be replicated across multiple channels. In order to maintainper-electrode charge balance, the return electrode in each pair cannotjust be switched to a supply rail (voltage source). The distribution ofimpedance, and therefore current, within the tissue is often not wellcontrolled, so current from the multiple current sources may flow to thereturn electrodes (connected to voltage sources) in an unpredictablemanner. For this reason, each stimulation channel will require both apositive (P) and a negative (N) current source, which are switchedbetween the two electrodes in an H-bridge manner.

This may also mean that the P and N current sources in each channel muchbe very accurately matched to each other; the idea of the weaker sourcelimiting the stronger will not work in this case, again because flow ofcurrent from multiple sources is not well controlled through tissue.Matching could be done by means of characterization during wafer-sortand trimming. It may also be possible to characterize and re-trim invivo, for example by using a small on-chip capacitor to accumulatecharge difference between the two sources during a non-stimulationcalibration phase. Note, however, that in order to trim to within, say,5 uA, an 8-bit DAC with a 10 mA full-scale output would require atrimming resolution on the order of ⅛ LSB. This may be a significantpractical issue.

One other possible approach may be to have two off-chip DC blockingcapacitors with switches to two active electrodes at a time, and alwaysuse monopolar stimulation, where current for both channels returns to asingle indifferent electrode.

6) Single-Point Failure Protection

As presented, the single- and multi-channel schemes in 4) and 5), above,do not protect against DC exposure in the case of a single-pointelectronic failure. This may even be true for the hybrid approach withthe single DC-blocking capacitor, since there is circuitry between thecapacitor and tissue. One approach to mitigating the risk may be to havea means to periodically monitor the “health” of the IC. The in vivo P-Ncalibration operation discussed in 5), above, could be performedperiodically to check for any bit failures within the DACs. In addition,leakage to electrode pads at the IC could be measured by using ahigh-value resistor that is switched into the circuit duringnon-stimulation intervals. This is shown by circuit diagram 7800 in FIG.78.

During a period of non-stimulation, say at startup and/or periodicallythereafter, all normal stimulation switches may be opened, and ahigh-value resistor is switched to one IC electrode pad at a time. Theopposite end of the resistor may be alternately switched to VDD andground, and the drop across the resistor measured with the on-chip ADCor a fixed-threshold comparator. Assuming a 10 megohm resistor, aleakage level of 10 nA will cause a 100 mV drop, which should notrequire heroic circuit design to measure. One drawback of this approachmay be the time required: if one assumes that the single-layercapacitance of the electrode interface will be in the circuit, the timeconstant will be on the order of 10 megohm*10 nF=0.1 s, meaning that itwill take on the order of 10 seconds to measure leakage on 8 electrodepads.

Another way to address single-fault failures (with the assumption thatthere are multiple potential failure points on-chip, as opposed to theidea that the entire chip is a single potential failure point) is toprovide redundancy in control circuits and blockage of potential leakagepaths. An example of this approach is shown by the circuit diagram 7900in FIG. 79.

Several mitigations are shown in diagram 7900. First, the mux switch canemploy redundancy in both transmission gates and controls. If onetransmission gate develops source-to-drain leakage, the other may stillblock current flow when it is disabled. Likewise, redundant digitalenable lines can prevent leakage if one is stuck on. Within eachtransmission gate, isolated well structures may be used and gate andbulk biases have very limited current drive, so that if a leakage defectoccurs, tissue exposure to DC current will be below the harm threshold.A similar approach could be used for pad ESD protection structures:redundant series low-side diodes and high-side clamps provide overallleakage protection even if one such device is leaky.

There may be a couple of drawbacks to these mitigations: One may besize—a redundant series transmission gate with the same ON resistance asa single, non-redundant gate will require four times the area; e.g., ifa 50 ohm complementary switch requires 0.1 mm² in a given high-voltageprocess, a 50 ohm redundant switch will require 0.4 mm². For the“hybrid” approach is section 5), two such switches per electrode arerequired, so the area required here may be prohibitive. Anotherpotential drawback may be that dual series high-side ESD clamps areprobably not available in standard ESD protections libraries, and solikely would have to be developed.

7) High-Frequency Current-Switching

Two papers by Liu, Demosthenous, and Donaldson, “In vitro evaluation ofa high-frequency current-switching stimulation technique for FESapplications” and “An Integrated Stimulator With DC-Isolation and FineCurrent Control for Implanted Nerve Tripoles” describe the use ofsmall-value, on-chip capacitors switched at high frequency to replacelarge DC blocking capacitors. In the first paper the authors claim thatthis approach both A) achieves charge-balanced stimulation and B)protects tissue against DC current in the event of a single-pointfailure. The general approach is shown by diagram 8000 in FIG. 80.

Capacitors C1 and C2 pump charge from the current source (IDAc) to theload, and as with any switched-cap circuit, capacitor size can be tradedoff for frequency, thus allowing small, on-chip capacitors.

The claim of charge-balance, A), however, may appear flawed for at leastthe following reason: In a conventional stimulator (a), a DC-blockingcapacitor may enforces charge balance because it is in both the chargeand discharge paths of the load, and so any imbalance between charge anddischarge phases results in a net voltage being developed across thecap, which will eventually limit current in one or the other phase andthus enforce charge balance. In the high-frequency current-switchingapproach, however, the capacitors' charge path may be through the loadbut the discharge path is not, so the capacitors cannot enforce chargebalance. The authors in fact achieve charge balance through passiveshorting after the stimulation pulse, and again referring to Sit'sthesis, there appears to some potential safety risk in relying onpassive shorting to provide more than just a minimal “fine adjustment”of charge balance.

In the second paper, the authors back away from the charge-balance claimbut provide substantiation for the single-point-failure-protection claimB). This appears somewhat more reasonable: The switched capacitors C1and C2 would limit DC leakage due to a failure in the positive currentsource, and the controls for the ground-return and discharge switchesare capacitively coupled, to avoid DC leakage paths in the case of afailure. However, the overall protection afforded seems limited:Switched capacitors behave like resistors in circuit, so while they willlimit maximum current in the case of a gross short, they will not limittotal charge delivered. Another issue is size; to achieve an equivalent50 ohm series resistance using a 5 Mhz switching frequency, C1 and C2would each have to have a value of 4 nf, requiring a total of 2 mm² ofarea in a typical process. This is roughly a factor of 5 larger than theredundant complementary switch discussed in section 6). In addition, theauthors use an SOI process to achieve supply isolation, so some workwould have to be done to see if sufficient isolation could be achievedusing a standard high-voltage bulk-CMOS process. (And availability ofdepletion-mode FETs are required in the process, to protect thecharge-balance function of the shorting switch in the case thatDDISCHAGE fails open.)

In short, because of the limited capabilities for both charge balancingand fault protection, this approach may not appear to be very promisingto replace large off-chip capacitors as safety elements.

8) Other Approaches

In their paper “Flexible Charge-Balanced Stimulator with 5.6 fC Accuracyfor 140 nC Injections” authors Nag, Jia, Thakor, and Sharma describe theuse of an H-bridge stimulator architecture with a single floatingcurrent source, as shown in the diagram 8100 in FIG. 81.

This may be similar to the simple single-channel stimulator described insection 4), above, in that a single current source is used for both thestimulation and recovery phases, and so ensures charge balance, assumingthe source is linear. This latter approach may use diodes instead ofswitches in some places, and so switch chip area could possibly betraded off with the fixed ˜0.7V drop of each diode (there is somequestion whether high-current on-chip Schottky diodes can be realizedpractically). However, to mux the single current source across multipleelectrode pairs, switches would still be required, so the saving mightbe moot. Also, issues of compliance limits, multi-channel simultaneousstimulation, and single-point failure protection are not addressed bythis design. Finally, the authors give no explanation of what isprobably the most challenging part of the design, i.e., how to design afloating current source. (On the other hand, they do detail themeasurement setup used to characterized charge balance accuracy of theirdesign).

In their paper “A voltage-controlled current source with regulatedelectrode bias-voltage for safe neural stimulation,” authors Schuettler,Franke, Krueger, and Stieglitz describe a purely analog approach that isvery elegant in its simplicity, but likely has practical limitations ina real application. The basic circuit is shown in the diagram 8200 inFIG. 82.

In this approach, amplifier C may integrate voltage across the loadusing a long time constant, and any non-zero average voltage (andtherefore current) acts as an error term that corrects the bipolarcurrent source. The primarily limitation to this approach may be thatthe DC accuracy required to ensure charge safety; assuming a target of10 nA net DC maximum and a 1 Kohm stimulation load, the circuit wouldhave to be accurate to 10 uV; this falls into the “heroics” category.Even if we use an additional shorting step to resolve small chargebalance errors, the circuit may still need to be accurate to a few mVs.A secondary issue may be that if we want to use a single positive powersupply node, the voltage measurement may have to be differential.

Finally, Cactus proposes the following current-sink H-bridge approachshown by circuit diagram 8300 in FIG. 83. This may be identical inprincipal to the simple single-channel stimulator described in 5),above. A difference may be in the use of an NFET (sink) current sourceinstead of a PFET source. Cactus's use of NFETs may likely beadvantageous in terms of chip area. On the other hand, PFETs are lessprone to issues with leakage due to impact ionization at high draincurrents/voltages. Also, the inventors here may find discomfort inconnecting the positive supply to tissue through a switch while the ESDdevices in the pads are connected to ground. Granted, it may require adouble-point failure to apply uncontrolled current to tissue, so thismay fall into the category of “superstition.”

The one point that Cactus may seem on slightly shaky ground is whetherthis can be scaled to multi-channel simultaneous stimulation; again, theproblem is one of per-electrode charge balance if more than oneelectrode is connected to a voltage source in a given stimulation phase.

While preferred embodiments of the present disclosure have been shownand described herein, it will be obvious to those skilled in the artthat such embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the scope of the present disclosure.It should be understood that various alternatives to the embodiments ofthe present disclosure described herein may be employed in practicingthe inventions of the present disclosure. It is intended that thefollowing claims define the scope of the invention and that methods andstructures within the scope of these claims and their equivalents becovered thereby.

1. (canceled)
 2. A neuromodulation apparatus comprising: (a) a tissuestimulator to stimulate tissue; and (b) means to periodically monitorcircuitry of the tissue stimulator to provide single-point failureprotection.
 3. The neuromodulation apparatus of claim 1, wherein themeans to periodically monitor circuitry of the tissue stimulator isconfigured to use a capacitor of the tissue stimulator to accumulatecharge during a calibration phase of the tissue stimulator to monitorthe tissue stimulator in vivo.
 4. The neuromodulation apparatus of claim1, wherein the means to periodically monitor circuitry of the tissuestimulator is configured to measure leakage of the tissue stimulatorwith a resistor of the tissue stimulator during a period ofnon-stimulation of the tissue stimulator.
 5. The neuromodulationapparatus of claim 1, wherein the tissue stimulator provides one or moreof control circuit redundancy or leakage path blockage.
 6. Theneuromodulation apparatus of claim 5, wherein the tissue stimulatorcomprises a mux switch to employ redundancy in a transmission or controlgate of the tissue stimulator to provide control circuit redundancy. 7.The neuromodulation apparatus of claim 5, wherein the tissue stimulatoris configured to digitally enable lines to prevent leakage if atransmission or control gate of the tissue stimulator becomes stuck. 8.The neuromodulation apparatus of claim 1, wherein the means toperiodically monitor circuitry of the tissue stimulator comprises one ormore isolated well structures in the tissue stimulator to limit acurrent drive of the tissue stimulator.
 9. The neuromodulation apparatusof claim 1, wherein the means to periodically monitor circuitry of thetissue stimulator is configured to ensure charge balance safety instimulating tissue.
 10. The neuromodulation apparatus of claim 9,wherein the means to periodically monitor circuitry of the tissuestimulator is configured to ensure charge balance safety duringstimulation of the tissue by the tissue stimulator by maintaining anactive charge balance between a first current source to stimulate tissueand a second current source to stimulate the tissue by matching thefirst and second current sources to operate in an H-bridge-likeconfiguration.
 11. The neuromodulation apparatus of claim 10, wherein:(a) the second current source is weaker than the first current sourceand a stimulation current of the tissue is determined by a current ofthe second current source; or (b) a mismatch between the first andsecond current sources is due to effective impedance and output directcurrent (DC) bias over at least two phases; or (c) the first and secondcurrent sources are cascoded and have parallel impedances of at least 1Mohm; or (d) the means to periodically monitor circuitry of the tissuestimulator is configured to drive individual sections sequentiallyduring recovery phases of one or more first or second current sources tominimize integral nonlinearity (INL) of one or more of the first orsecond current sources.
 12. The neuromodulation apparatus of claim 9,wherein the means to periodically monitor circuitry of the tissuestimulator is configured to ensure charge balance safety byshort-circuiting one or more electrodes of the tissue stimulator toremove residual charge during stimulation of the tissue with the one ormore electrodes.
 13. The neuromodulation apparatus of claim 12, wherein:(a) short-circuiting the one or more electrodes comprisesshort-circuiting the one or more electrodes for a time interval of 3 ormore time constants during a non-stimulation phase of the one or moreelectrodes; or (b) short-circuiting the one or more electrodes comprisesshort-circuiting the one or more electrodes when Faradic resistance ofthe one or more electrodes is greater than 1 Mohm.
 14. Theneuromodulation apparatus of claim 9, wherein the means to periodicallymonitor circuitry of the tissue stimulator is configured to ensurecharge balance safety by monitoring and controlling a current of thetissue stimulator to minimize a voltage compliance effect on currentbalancing of the tissue stimulator during stimulation by the tissuestimulator.
 15. The neuromodulation apparatus of claim 14, wherein: (a)monitoring and controlling the current comprises providing a providing avoltage detection circuit at a current source output of the tissuestimulator; or (b) monitoring and controlling the current comprisesturning off a current source of the tissue stimulator when the currentis outside a compliance range; or (c) monitoring and controlling thecurrent comprises providing a safety margin of compliance detection toensure a current source of the tissue stimulator is stopped in a linearrange.
 16. The neuromodulation apparatus of claim 9, wherein the meansto periodically monitor circuitry of the tissue stimulator is configuredto ensure by maintaining an active charge balance with current source tostimulate tissue operating in an H-bridge-like configuration duringstimulation of the tissue by the tissue stimulator.
 17. Theneuromodulation apparatus of claim 16, wherein maintaining the activecharge balance comprises maintaining an operation of the current sourcein a linear region to ensure equal current in stimulation and recoveryphases of the current source.
 18. The neuromodulation apparatus of claim16, wherein the tissue stimulator is configured to stimulate the tissuewith multiple single current sources operating in the H-bridge likeconfiguration and recovering the multiple single current sourcessequentially, optionally wherein the tissue stimulator is configured tostimulate tissue with the multiple single current sources by providingstimulation current to two or more active electrodes with a singlesource or return path in the tissue stimulator.
 19. The neuromodulationapparatus of claim 9, wherein the means to periodically monitorcircuitry of the tissue comprises a single off-chip DC blockingcapacitor of the tissue stimulator connectable to at least one electrodeof the tissue stimulator through a switch during stimulation by thetissue stimulator optionally further comprising an energy storagecapacitor in the DC blocking capacitor.
 20. The neuromodulationapparatus of claim 9, wherein the means to periodically monitorcircuitry of the tissue is configured to ensure charge balance safety byensuring that, during stimulation by the tissue stimulator, a recoveryphase of the tissue stimulator does not forward bias ESD electrodes ofthe tissue stimulator by grounding switches of the tissue stimulatorthat behave like linear loads.
 21. The neuromodulation apparatus ofclaim 9, wherein the tissue stimulator is configured to stimulate thetissue with multiple-channels with a plurality of current sources of thetissue stimulator that are precisely matched with one another, wherein:(a) the plurality of current sources are matched with one another duringwafer sort and trimming of the tissue stimulator; or (b) the tissuestimulator is configured to stimulate the tissue with the preciselymatched current sources by re-trimming the tissue stimulator in vivousing a capacitor of the tissue stimulator to accumulate charge during acalibration phase of the capacitor; or (c) the tissue stimulator isconfigured to stimulate the tissue with the precisely matched currentsources by providing two or more off-chip capacitors with switches totwo active electrodes with a single return path in the tissuestimulator.